7-96488606-G-T

Variant names:

• chr7-96488606-G-T
• rs4729260
• ENST00000611360.4:n.87-2189C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000611360.4(SEM1):​n.87-2189C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 30)
• Consequence: SEM1 ENST00000611360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 27 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]

LOC105375411 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEM1	NR_163948.1	n.100-2189C>A		intron_variant	Intron 2 of 4
SEM1	NR_163949.1	n.100-2189C>A		intron_variant	Intron 2 of 3
SEM1	NR_163950.1	n.537-2189C>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEM1	ENST00000611360.4	n.87-2189C>A		intron_variant	Intron 2 of 3	1
SEM1	ENST00000356686.2	c.13-2189C>A		intron_variant	Intron 1 of 3	5		ENSP00000349114.1
SEM1	ENST00000615352.4	c.13-2189C>A		intron_variant	Intron 1 of 2	5		ENSP00000481021.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151756 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151756 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74056

African (AFR) AF: 0.00 AC: 0 AN: 41300

American (AMR) AF: 0.0000657 AC: 1 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 16316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs4729260; hg19: chr7-96117918;