rs7659335

Positions:

• chr4-164768514-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352885.1(SMIM31):​c.-25-1905T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,036 control chromosomes in the GnomAD database, including 18,200 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18200 hom., cov: 29)
• Consequence: SMIM31 NM_001352885.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

Genes affected

SMIM31 (HGNC:49638): (small integral membrane protein 31) Predicted to be located in axon. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM31	NM_001352885.1	c.-25-1905T>C		intron_variant		ENST00000507311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM31	ENST00000507311.1	c.-25-1905T>C		intron_variant		1	NM_001352885.1	P1
SMIM31	ENST00000515485.5	c.-25-1905T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72141 AN: 150930 Hom.: 18181 Cov.: 29

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.478 AC: 72169 AN: 151036 Hom.: 18200 Cov.: 29 AF XY: 0.474 AC XY: 34942 AN XY: 73686

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.449

Alfa AF: 0.514 Hom.: 2550

Bravo AF: 0.480

Asia WGS AF: 0.446 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7659335; hg19: chr4-165689666;