NM_001141917.2:c.3971G>A

Variant names:

• chr9-34723269-C-T
• rs367965087
• NM_001141917.2:c.3971G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001141917.2(SPATA31F1):​c.3971G>A​(p.Arg1324Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000541 in 1,551,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (1 hom.)
• Consequence: SPATA31F1 NM_001141917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037917763).

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.3971G>A	p.Arg1324Gln	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.3971G>A	p.Arg1324Gln	missense	Exon 4 of 4	ENSP00000417711.1	Q6ZU69
	ENSG00000230074	ENST00000664167.1		n.86+20231C>T		intron	N/A
	ENSG00000230074	ENST00000837930.1		n.174+20231C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000961 AC: 15 AN: 156146 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000243

Gnomad ASJ exome AF: 0.000590

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000663

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000565 AC: 79 AN: 1399412 Hom.: 1 Cov.: 64 AF XY: 0.0000666 AC XY: 46 AN XY: 690208

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.000364 AC: 13 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.000715 AC: 18 AN: 25176

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49282

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5694

European-Non Finnish (NFE) AF: 0.0000352 AC: 38 AN: 1078976

Other (OTH) AF: 0.000121 AC: 7 AN: 58012

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74478

African (AFR) AF: 0.0000241 AC: 1 AN: 41560

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000205 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000314 AC: 1

ExAC AF: 0.0000753 AC: 2

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	0.087
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.6
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.024
Sift	Benign	0.062	T
Sift4G	Benign	0.068	T
Polyphen		0.87	P
Vest4		0.10
MVP		0.072
ClinPred		0.039	T
GERP RS		-1.9
Varity_R		0.034
gMVP		0.062
Mutation Taster		=100/0	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: rs367965087; hg19: chr9-34723266; COSMIC: COSV105326539;