rs3801293

Variant names:

• chr7-96695187-G-A
• rs3801293
• NM_006304.2:c.77-296C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006304.2(SEM1):​c.77-296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 211,174 control chromosomes in the GnomAD database, including 3,195 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 0.17 (2215 hom., cov: 32)
  • Exomes 𝑓: 0.17 (980 hom.)
• Consequence: SEM1 NM_006304.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 5 publications found

Genes affected

SEM1 (HGNC:10845): (SEM1 26S proteasome subunit) The product of this gene has been localized within the split hand/split foot malformation locus SHFM1 at chromosome 7. It has been proposed to be a candidate gene for the autosomal dominant form of the heterogeneous limb developmental disorder split hand/split foot malformation type 1. In addition, it has been shown to directly interact with BRCA2. It also may play a role in the completion of the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEM1	NM_006304.2	c.77-296C>T		intron_variant	Intron 1 of 2	ENST00000248566.4	NP_006295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEM1	ENST00000248566.4	c.77-296C>T		intron_variant	Intron 1 of 2	1	NM_006304.2	ENSP00000248566.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25719 AN: 151460 Hom.: 2211 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.173 AC: 10317 AN: 59594 Hom.: 980 Cov.: 0 AF XY: 0.173 AC XY: 5343 AN XY: 30892

African (AFR) AF: 0.152 AC: 302 AN: 1990

American (AMR) AF: 0.185 AC: 411 AN: 2226

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 364 AN: 2288

East Asian (EAS) AF: 0.173 AC: 797 AN: 4596

South Asian (SAS) AF: 0.204 AC: 509 AN: 2498

European-Finnish (FIN) AF: 0.210 AC: 610 AN: 2906

Middle Eastern (MID) AF: 0.162 AC: 45 AN: 278

European-Non Finnish (NFE) AF: 0.171 AC: 6627 AN: 38790

Other (OTH) AF: 0.162 AC: 652 AN: 4022

GnomAD4 genome AF: 0.170 AC: 25748 AN: 151580 Hom.: 2215 Cov.: 32 AF XY: 0.173 AC XY: 12846 AN XY: 74054

African (AFR) AF: 0.148 AC: 6117 AN: 41418

American (AMR) AF: 0.173 AC: 2640 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 511 AN: 3454

East Asian (EAS) AF: 0.188 AC: 968 AN: 5162

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4820

European-Finnish (FIN) AF: 0.224 AC: 2364 AN: 10534

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11651 AN: 67662

Other (OTH) AF: 0.170 AC: 357 AN: 2106

Alfa AF: 0.169 Hom.: 397

Bravo AF: 0.165

Asia WGS AF: 0.236 AC: 818 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs3801293; hg19: chr7-96324499;