NM_001289970.2:c.*46G>T

Variant names:

• chr5-171791134-G-T
• rs7718767
• NM_001289970.2:c.*46G>T

Variant summary

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

The NM_001289970.2(SMIM23):​c.*46G>T variant causes a splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMIM23 NM_001289970.2 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 4 publications found

Genes affected

SMIM23 (HGNC:34440): (small integral membrane protein 23) Predicted to be located in plasma membrane. 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=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289970.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM23	NM_001289970.2	MANE Select	c.*46G>T		splice_region	Exon 4 of 4	NP_001276899.1	A6NLE4
	SMIM23	NM_001289970.2	MANE Select	c.*46G>T		3_prime_UTR	Exon 4 of 4	NP_001276899.1	A6NLE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM23	ENST00000523047.4	TSL:2 MANE Select	c.*46G>T		splice_region	Exon 4 of 4	ENSP00000430818.4	A6NLE4
	SMIM23	ENST00000523047.4	TSL:2 MANE Select	c.*46G>T		3_prime_UTR	Exon 4 of 4	ENSP00000430818.4	A6NLE4
	SMIM23	ENST00000639838.1	TSL:5	n.*46G>T		non_coding_transcript_exon	Exon 4 of 8	ENSP00000490990.1	A6NLE4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 5691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.2
DANN	Benign	0.88
PhyloP100		-0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7718767; hg19: chr5-171218138;