1-3775433-AGTCAGCCTAGGGGCTGT-A

Position:

• chr1-3775433-AGTCAGCCTAGGGGCTGT-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001288583.2(SMIM1):​c.64_80delAGCCTAGGGGCTGTGTC​(p.Ser22fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,548,528 control chromosomes in the GnomAD database, including 165 homozygotes. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.0091 (10 hom., cov: 31)
  • Exomes 𝑓: 0.012 (155 hom.)
• Consequence: SMIM1 NM_001288583.2 frameshift
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 1.75

Genes affected

SMIM1 (HGNC:44204): (small integral membrane protein 1 (Vel blood group)) This gene encodes a small, conserved protein that participates in red blood cell formation. The encoded protein is localized to the cell membrane and is the antigen for the Vel blood group. Alternative splicing results in different transcript variants that encode the same protein. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 10 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM1	NM_001288583.2	c.64_80delAGCCTAGGGGCTGTGTC	p.Ser22fs	frameshift_variant	3/4	ENST00000642557.4	NP_001275512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMIM1	ENST00000642557.4	c.64_80delAGCCTAGGGGCTGTGTC	p.Ser22fs	frameshift_variant	3/4		NM_001288583.2	ENSP00000496314.2
SMIM1	ENST00000444870.7	c.64_80delAGCCTAGGGGCTGTGTC	p.Ser22fs	frameshift_variant	3/4	1		ENSP00000457386.1
SMIM1	ENST00000561886.2	c.64_80delAGCCTAGGGGCTGTGTC	p.Ser22fs	frameshift_variant	3/3	2		ENSP00000456559.1
SMIM1	ENST00000452264.1	c.*46_*62delGTCAGCCTAGGGGCTGT		downstream_gene_variant		2		ENSP00000457674.1

Frequencies

GnomAD3 genomes AF: 0.00910 AC: 1383 AN: 151956 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0122 AC: 17003 AN: 1396454 Hom.: 155 AF XY: 0.0120 AC XY: 8263 AN XY: 688710

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00608

Gnomad4 ASJ exome AF: 0.00414

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.00190

Gnomad4 FIN exome AF: 0.00827

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.00910 AC: 1384 AN: 152074 Hom.: 10 Cov.: 31 AF XY: 0.00871 AC XY: 648 AN XY: 74358

Gnomad4 AFR AF: 0.00263

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00613

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0112 Hom.: 5

Bravo AF: 0.00923

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Vel blood group system Other:1

Affects, no assertion criteria provided

literature only

OMIM

May 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs566629828; hg19: chr1-3691997;