rs472644

Variant names:

• chr9-34724062-G-A
• rs472644
• NM_001141917.2:c.3178C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-34724062-G-A
• chr9-34724062-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63
• Publications: 13 publications found

Genes affected

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

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]

ENSG00000230074 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31F1	NM_001141917.2	MANE Select	c.3178C>T	p.His1060Tyr	missense	Exon 4 of 4	NP_001135389.1	Q6ZU69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31F1	ENST00000378788.4	TSL:2 MANE Select	c.3178C>T	p.His1060Tyr	missense	Exon 4 of 4	ENSP00000417711.1	Q6ZU69
	ENSG00000230074	ENST00000664167.1		n.86+21024G>A		intron	N/A
	ENSG00000230074	ENST00000837930.1		n.174+21024G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.385 AC: 57158 AN: 148460 Hom.: 13170 Cov.: 26

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

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.: 41 AF XY: 0.458 AC XY: 232097 AN XY: 506440

⚠️ 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), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.385 AC: 57183 AN: 148580 Hom.: 13177 Cov.: 26 AF XY: 0.387 AC XY: 28011 AN XY: 72324

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

Alfa AF: 0.437 Hom.: 5962

Bravo AF: 0.373

ExAC AF: 0.290 AC: 7015

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.1
DANN	Benign	0.97
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Uncertain	0.035	D
Polyphen		0.67	P
Vest4		0.040
ClinPred		0.011	T
GERP RS		3.2
Varity_R		0.025
gMVP		0.069
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs472644; hg19: chr9-34724059; COSMIC: COSV66488496;