9-34725745-T-C

Variant names:

• chr9-34725745-T-C
• rs62547039
• NM_001141917.2:c.1495A>G

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.1495A>G​(p.Met499Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,546,872 control chromosomes in the GnomAD database, including 346,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M499I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.64 (30375 hom., cov: 28)
  • Exomes 𝑓: 0.67 (316478 hom.)
• Consequence: SPATA31F1 NM_001141917.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497
• Publications: 23 publications found

Genes affected

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

ENSG00000230074 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.1892371E-6).
• BP6: Variant 9-34725745-T-C is Benign according to our data. Variant chr9-34725745-T-C is described in ClinVar as Benign. ClinVar VariationId is 402844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31F1	NM_001141917.2	c.1495A>G	p.Met499Val	missense_variant	Exon 4 of 4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1	c.133+22707T>C		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1	c.70+22707T>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	c.1495A>G	p.Met499Val	missense_variant	Exon 4 of 4	2	NM_001141917.2	ENSP00000417711.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 96792 AN: 150538 Hom.: 30357 Cov.: 28

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.629

GnomAD2 exomes AF: 0.682 AC: 104811 AN: 153610 AF XY: 0.693

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.652

Gnomad EAS exome AF: 0.676

Gnomad FIN exome AF: 0.692

Gnomad NFE exome AF: 0.667

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.674 AC: 940789 AN: 1396222 Hom.: 316478 Cov.: 71 AF XY: 0.678 AC XY: 466156 AN XY: 687998

African (AFR) AF: 0.554 AC: 17420 AN: 31462

American (AMR) AF: 0.660 AC: 23513 AN: 35652

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 16351 AN: 25066

East Asian (EAS) AF: 0.675 AC: 24084 AN: 35660

South Asian (SAS) AF: 0.790 AC: 62442 AN: 79084

European-Finnish (FIN) AF: 0.702 AC: 34552 AN: 49202

Middle Eastern (MID) AF: 0.687 AC: 3903 AN: 5684

European-Non Finnish (NFE) AF: 0.668 AC: 719433 AN: 1076556

Other (OTH) AF: 0.676 AC: 39091 AN: 57856

GnomAD4 genome AF: 0.643 AC: 96855 AN: 150650 Hom.: 30375 Cov.: 28 AF XY: 0.646 AC XY: 47511 AN XY: 73528

African (AFR) AF: 0.569 AC: 23302 AN: 40930

American (AMR) AF: 0.621 AC: 9415 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2189 AN: 3460

East Asian (EAS) AF: 0.689 AC: 3422 AN: 4964

South Asian (SAS) AF: 0.779 AC: 3697 AN: 4746

European-Finnish (FIN) AF: 0.704 AC: 7334 AN: 10424

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45300 AN: 67684

Other (OTH) AF: 0.631 AC: 1320 AN: 2092

Alfa AF: 0.660 Hom.: 17013

Bravo AF: 0.629

ExAC AF: 0.655 AC: 16485

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	0.060
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.054
DANN	Benign	0.33
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.061	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.50
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0070
ClinPred		0.00043	T
GERP RS		-1.3
Varity_R		0.044
gMVP		0.086
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: rs62547039; hg19: chr9-34725742; COSMIC: COSV66488350;