9-34724062-G-A

Position:

• chr9-34724062-G-A

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]

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]

ENSG00000288583 (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	Protein	UniProt
SPATA31F1	NM_001141917.2	c.3178C>T	p.His1060Tyr	missense_variant	4/4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1	c.133+21024G>A		intron_variant			XP_047279058.1
PHF24	XM_047423103.1	c.70+21024G>A		intron_variant			XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM205A	ENST00000378788.4	c.3178C>T	p.His1060Tyr	missense_variant	4/4	2	NM_001141917.2	ENSP00000417711.1
ENSG00000288583	ENST00000664167.1	n.86+21024G>A		intron_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
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;