rs472644

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

Genes affected

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

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SPATA31F1	NM_001141917.2	c.3178C>T	p.His1060Tyr	missense_variant	4/4	ENST00000378788.4
PHF24	XM_047423102.1	c.133+21024G>A		intron_variant
PHF24	XM_047423103.1	c.70+21024G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA31F1	ENST00000378788.4	c.3178C>T	p.His1060Tyr	missense_variant	4/4	2	NM_001141917.2	P1
	ENST00000664167.1	n.86+21024G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.387 AC: 45115 AN: 116532 Hom.: 11907 AF XY: 0.384 AC XY: 22985 AN XY: 59884

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 SAS exome AF: 0.378

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

Gnomad4 AFR exome AF: 0.0711

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.631

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.437

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.392

Alfa AF: 0.418 Hom.: 3102

Bravo AF: 0.373

ExAC AF: 0.290 AC: 7015

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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	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
MutationTaster	Benign	1.0	P
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

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

LitVar

Other links and lift over

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