NM_001141917.2:c.3562G>T

Variant names:

• chr9-34723678-C-A
• rs476287
• NM_001141917.2:c.3562G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001141917.2(SPATA31F1):​c.3562G>T​(p.Gly1188Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,551,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1188D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: SPATA31F1 NM_001141917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.48
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14347142).

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.3562G>T	p.Gly1188Cys	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.3562G>T	p.Gly1188Cys	missense	Exon 4 of 4	ENSP00000417711.1	Q6ZU69
	ENSG00000230074	ENST00000664167.1		n.86+20640C>A		intron	N/A
	ENSG00000230074	ENST00000837930.1		n.174+20640C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000153 AC: 24 AN: 156474 AF XY: 0.000193

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000119

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.000182 AC: 255 AN: 1399270 Hom.: 0 Cov.: 66 AF XY: 0.000196 AC XY: 135 AN XY: 690146

African (AFR) AF: 0.0000316 AC: 1 AN: 31596

American (AMR) AF: 0.000252 AC: 9 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.0000794 AC: 2 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79234

European-Finnish (FIN) AF: 0.0000813 AC: 4 AN: 49194

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5694

European-Non Finnish (NFE) AF: 0.000207 AC: 223 AN: 1078938

Other (OTH) AF: 0.000224 AC: 13 AN: 58002

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.000262 AC: 4 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000242

ExAC AF: 0.0000408 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.5
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.019
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.16
MVP		0.32
ClinPred		0.14	T
GERP RS		-0.22
Varity_R		0.22
gMVP		0.14
Mutation Taster		=98/2	polymorphism

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: rs476287; hg19: chr9-34723675; COSMIC: COSV105326534;