rs201220429

Variant names:

• chr9-34723372-C-G
• rs201220429
• NM_001141917.2:c.3868G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001141917.2(SPATA31F1):​c.3868G>C​(p.Asp1290His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000664 in 1,551,578 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: SPATA31F1 NM_001141917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.579
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0076422393).

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.3868G>C	p.Asp1290His	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.3868G>C	p.Asp1290His	missense	Exon 4 of 4	ENSP00000417711.1	Q6ZU69
	ENSG00000230074	ENST00000664167.1		n.86+20334C>G		intron	N/A
	ENSG00000230074	ENST00000837930.1		n.174+20334C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00231

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: 0.00

GnomAD2 exomes AF: 0.000211 AC: 33 AN: 156434 AF XY: 0.000277

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000810

Gnomad ASJ exome AF: 0.00294

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000661

Gnomad OTH exome AF: 0.000455

GnomAD4 exome AF: 0.0000665 AC: 93 AN: 1399414 Hom.: 0 Cov.: 67 AF XY: 0.0000869 AC XY: 60 AN XY: 690214

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

American (AMR) AF: 0.0000560 AC: 2 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00274 AC: 69 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1078980

Other (OTH) AF: 0.000155 AC: 9 AN: 58002

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000405 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.000270 AC: 7

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	-0.45	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.58
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.011
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.078	T
Polyphen		0.97	D
Vest4		0.11
MVP		0.12
ClinPred		0.082	T
GERP RS		0.95
Varity_R		0.061
gMVP		0.13
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: rs201220429; hg19: chr9-34723369;