rs10429035

Positions:

• chr7-96490169-G-A

Variant summary

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

The ENST00000356686.2(SEM1):​c.13-3752C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,920 control chromosomes in the GnomAD database, including 13,277 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 0.38 (13277 hom., cov: 32)
• Consequence: SEM1 ENST00000356686.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561

Genes affected

SEM1 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEM1	NR_163948.1	n.100-3752C>T		intron_variant
SEM1	NR_163949.1	n.100-3752C>T		intron_variant
SEM1	NR_163950.1	n.537-3752C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEM1	ENST00000611360.4	n.87-3752C>T		intron_variant		1
SEM1	ENST00000356686.2	c.13-3752C>T		intron_variant		5		ENSP00000349114.1
SEM1	ENST00000615352.4	c.13-3752C>T		intron_variant		5		ENSP00000481021.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57543 AN: 151802 Hom.: 13231 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.379 AC: 57644 AN: 151920 Hom.: 13277 Cov.: 32 AF XY: 0.379 AC XY: 28110 AN XY: 74258

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.370

Alfa AF: 0.285 Hom.: 9805

Bravo AF: 0.389

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10429035; hg19: chr7-96119481;