Genetic Variant SPATA31F1:p.His1060Asp (chr9-34724062-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001141917.2(SPATA31F1):c.3178C>G(p.His1060Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1060Y) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 26)

Failed GnomAD Quality Control

Consequence

SPATA31F1
NM_001141917.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10182601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SPATA31F1	NM_001141917.2 link	c.3178C>G	p.His1060Asp	missense_variant	Exon 4 of 4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1 link	c.133+21024G>C		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1 link	c.70+21024G>C		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>G	p.His1060Asp	missense_variant	Exon 4 of 4	2	NM_001141917.2	ENSP00000417711.1		Q6ZU69

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149778

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72884

African (AFR)

AF:

0.00

AC:

AN:

41208

American (AMR)

AF:

0.00

AC:

AN:

14982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4950

South Asian (SAS)

AF:

0.00

AC:

AN:

4564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67104

Other (OTH)

AF:

0.00

AC:

AN:

2050

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.017

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.56

M_CAP

Benign

0.0090

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

1.6

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.048

Sift

Benign

0.21

Sift4G

Uncertain

0.031

Polyphen

0.93

Vest4

0.21

MutPred

0.15

Loss of helix (P = 0.0376);

MVP

0.072

ClinPred

0.35

GERP RS

3.2

Varity_R

0.078

gMVP

0.10

Mutation Taster

=98/2

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over