22-41948262-A-T

Variant names:

• chr22-41948262-A-T
• rs5996091
• NM_001395946.1:c.-15+956A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395946.1(SMIM45):​c.-15+956A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: SMIM45 NM_001395946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 9 publications found

Genes affected

SMIM45 (HGNC:27930): (small integral membrane protein 45) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM45	NM_001395946.1	c.-15+956A>T		intron_variant	Intron 1 of 1		NP_001382875.1
SMIM45	NM_001395947.1	c.-15+454A>T		intron_variant	Intron 1 of 1		NP_001382876.1
SMIM45	NM_001395948.1	c.-152+956A>T		intron_variant	Intron 1 of 2		NP_001382877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM45	ENST00000711329.1	c.-15+956A>T		intron_variant	Intron 1 of 1			ENSP00000518693.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.79
PhyloP100		0.75

Splicing

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

Other links and lift over

dbSNP: rs5996091; hg19: chr22-42344266;