11-1747849-C-T

Position:

• chr11-1747849-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170820.4(IFITM10):​c.355G>A​(p.Ala119Thr) variant causes a missense 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. 14/20 in silico tools predict 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: 33)
• Consequence: IFITM10 NM_001170820.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

Genes affected

IFITM10 (HGNC:40022): (interferon induced transmembrane protein 10) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250644 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03632915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFITM10	NM_001170820.4	c.355G>A	p.Ala119Thr	missense_variant	2/3	ENST00000340134.5	NP_001164291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFITM10	ENST00000340134.5	c.355G>A	p.Ala119Thr	missense_variant	2/3	3	NM_001170820.4	ENSP00000344430.4
ENSG00000250644	ENST00000636615.1	c.1342G>A	p.Ala448Thr	missense_variant	9/10	5		ENSP00000490014.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.30
DANN	Benign	0.92
DEOGEN2	Benign	0.015	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.19	N;.;.
REVEL	Benign	0.010
Sift	Benign	0.37	T;.;.
Sift4G	Benign	0.24	T;.;.
Vest4		0.054
MutPred		0.17		Gain of glycosylation at A119 (P = 0.0037);.;.;
MVP		0.030
ClinPred		0.066	T
GERP RS		-3.5
Varity_R		0.037
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs903221780; hg19: chr11-1769079;