11-118004456-C-T

Variant names:

• chr11-118004456-C-T
• rs4938467
• NM_001394165.1:c.*1954G>A

Variant summary

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

The NM_001394165.1(SMIM35):​c.*1954G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,898 control chromosomes in the GnomAD database, including 19,620 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 0.51 (19613 hom., cov: 31)
  • Exomes 𝑓: 0.37 (7 hom.)
• Consequence: SMIM35 NM_001394165.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 6 publications found

Genes affected

SMIM35 (HGNC:44179): (small integral membrane protein 35) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394165.1. 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
	SMIM35	NM_001394165.1	MANE Select	c.*1954G>A		3_prime_UTR	Exon 5 of 5	NP_001381094.1
	SMIM35	NM_001394164.1		c.*1954G>A		3_prime_UTR	Exon 6 of 6	NP_001381093.1
	SMIM35	NM_001394166.1		c.*1954G>A		3_prime_UTR	Exon 4 of 4	NP_001381095.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM35	ENST00000689828.1	MANE Select	c.*1954G>A		3_prime_UTR	Exon 5 of 5	ENSP00000509259.1
	SMIM35	ENST00000636151.1	TSL:5	c.*1998G>A		3_prime_UTR	Exon 7 of 7	ENSP00000490666.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76896 AN: 151674 Hom.: 19600 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.368 AC: 39 AN: 106 Hom.: 7 Cov.: 0 AF XY: 0.339 AC XY: 21 AN XY: 62

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.348 AC: 23 AN: 66

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.542 AC: 13 AN: 24

Other (OTH) AF: 0.214 AC: 3 AN: 14

GnomAD4 genome AF: 0.507 AC: 76945 AN: 151792 Hom.: 19613 Cov.: 31 AF XY: 0.508 AC XY: 37673 AN XY: 74174

African (AFR) AF: 0.516 AC: 21344 AN: 41338

American (AMR) AF: 0.577 AC: 8811 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3470

East Asian (EAS) AF: 0.592 AC: 3046 AN: 5146

South Asian (SAS) AF: 0.547 AC: 2629 AN: 4804

European-Finnish (FIN) AF: 0.408 AC: 4289 AN: 10524

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33220 AN: 67938

Other (OTH) AF: 0.534 AC: 1121 AN: 2098

Alfa AF: 0.443 Hom.: 2309

Bravo AF: 0.520

Asia WGS AF: 0.583 AC: 2025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.80
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs4938467; hg19: chr11-117875171;