rs928482

chr6-34247444-G-Achr6-34247444-G-T

Variant summary

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

The NM_001008703.4(SMIM29):c.137+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,571,942 control chromosomes in the GnomAD database, including 8,149 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 0.13 (2714 hom., cov: 32)
  • Exomes 𝑓: 0.051 (5435 hom.)
• Consequence: SMIM29 NM_001008703.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

SMIM29 (HGNC:1340): (small integral membrane protein 29) Predicted to be integral component of membrane. [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 (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM29	NM_001008703.4	c.137+23C>T		intron_variant		ENST00000476320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM29	ENST00000476320.6	c.137+23C>T		intron_variant		2	NM_001008703.4	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20335 AN: 151960 Hom.: 2696 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0409

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.108 AC: 20247 AN: 186898 Hom.: 2697 AF XY: 0.0930 AC XY: 9226 AN XY: 99180

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.0486

Gnomad EAS exome AF: 0.120

Gnomad SAS exome AF: 0.0413

Gnomad FIN exome AF: 0.0210

Gnomad NFE exome AF: 0.0355

Gnomad OTH exome AF: 0.0863

GnomAD4 exome AF: 0.0507 AC: 71970 AN: 1419864 Hom.: 5435 Cov.: 36 AF XY: 0.0490 AC XY: 34380 AN XY: 701984

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.0493

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0403

Gnomad4 FIN exome AF: 0.0199

Gnomad4 NFE exome AF: 0.0301

Gnomad4 OTH exome AF: 0.0663

GnomAD4 genome AF: 0.134 AC: 20397 AN: 152078 Hom.: 2714 Cov.: 32 AF XY: 0.133 AC XY: 9901 AN XY: 74334

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.0168

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0491 Hom.: 204

Bravo AF: 0.162

Asia WGS AF: 0.0980 AC: 340 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	0.11
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs928482; hg19: chr6-34215221; COSMIC: COSV58988198; COSMIC: COSV58988198;