rs472644

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001141917.2(SPATA31F1):c.3178C>T(p.His1060Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,166,718 control chromosomes in the GnomAD database, including 170,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 13177 hom., cov: 26)

Exomes 𝑓: 0.46 ( 157510 hom. )

Consequence

SPATA31F1
NM_001141917.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

Publications

13 publications found

Variant links:

Genes affected

SPATA31F1 (HGNC:41911): (SPATA31 subfamily F member 1) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31F1 links:

ENSG00000230074 (HGNC:):

ENSG00000230074 links:

PHF24 (HGNC:29180): (PHD finger protein 24) Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including detection of mechanical stimulus involved in sensory perception of pain; gamma-aminobutyric acid signaling pathway; and regulation of GABAergic synaptic transmission. [provided by Alliance of Genome Resources, Apr 2022]

PHF24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5235513E-5).

BP6

Variant 9-34724062-G-A is Benign according to our data. Variant chr9-34724062-G-A is described in ClinVar as Benign. ClinVar VariationId is 402843.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SPATA31F1	NM_001141917.2 link	c.3178C>T	p.His1060Tyr	missense_variant	Exon 4 of 4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1 link	c.133+21024G>A		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1 link	c.70+21024G>A		intron_variant	Intron 2 of 9		XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31F1	ENST00000378788.4 link	c.3178C>T	p.His1060Tyr	missense_variant	Exon 4 of 4	2	NM_001141917.2	ENSP00000417711.1		Q6ZU69

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

57158

AN:

148460

Hom.:

13170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.518

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.386

GnomAD2 exomes

AF:

0.387

AC:

45115

AN:

116532

AF XY:

0.384

show subpopulations

Gnomad AFR exome

AF:

0.0951

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.413

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.458

AC:

466799

AN:

1018138

Hom.:

157510

Cov.:

AF XY:

0.458

AC XY:

232097

AN XY:

506440

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0711

AC:

2079

AN:

29220

American (AMR)

AF:

0.417

AC:

12145

AN:

29130

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

6273

AN:

21116

East Asian (EAS)

AF:

0.631

AC:

21335

AN:

33836

South Asian (SAS)

AF:

0.493

AC:

31719

AN:

64330

European-Finnish (FIN)

AF:

0.491

AC:

21549

AN:

43886

Middle Eastern (MID)

AF:

0.353

AC:

1590

AN:

4500

European-Non Finnish (NFE)

AF:

0.469

AC:

350316

AN:

746832

Other (OTH)

AF:

0.437

AC:

19793

AN:

45288

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.357

Heterozygous variant carriers

7241

14481

21722

28962

36203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7044

14088

21132

28176

35220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.385

AC:

57183

AN:

148580

Hom.:

13177

Cov.:

AF XY:

0.387

AC XY:

28011

AN XY:

72324

show subpopulations

African (AFR)

AF:

0.123

AC:

5071

AN:

41150

American (AMR)

AF:

0.416

AC:

6154

AN:

14784

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1182

AN:

3428

East Asian (EAS)

AF:

0.618

AC:

3024

AN:

4892

South Asian (SAS)

AF:

0.519

AC:

2345

AN:

4518

European-Finnish (FIN)

AF:

0.500

AC:

5073

AN:

10142

Middle Eastern (MID)

AF:

0.355

AC:

103

AN:

290

European-Non Finnish (NFE)

AF:

0.498

AC:

33114

AN:

66446

Other (OTH)

AF:

0.392

AC:

799

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

1386

2773

4159

5546

6932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.437

Hom.:

5962

Bravo

AF:

0.373

ExAC

AF:

0.290

AC:

7015

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.1

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.65

MetaRNN

Benign

0.000025

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

1.6

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.59

REVEL

Benign

0.065

Sift

Benign

1.0

Sift4G

Uncertain

0.035

Polyphen

0.67

Vest4

0.040

ClinPred

0.011

GERP RS

3.2

Varity_R

0.025

gMVP

0.069

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over