chr11-1747789-T-A

Position:

• chr11-1747789-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001170820.4(IFITM10):​c.415A>T​(p.Thr139Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: IFITM10 NM_001170820.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFITM10	NM_001170820.4	c.415A>T	p.Thr139Ser	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.415A>T	p.Thr139Ser	missense_variant	2/3	3	NM_001170820.4	ENSP00000344430.4
ENSG00000250644	ENST00000636615.1	c.1402A>T	p.Thr468Ser	missense_variant	9/10	5		ENSP00000490014.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.415A>T (p.T139S) alteration is located in exon 2 (coding exon 2) of the IFITM10 gene. This alteration results from a A to T substitution at nucleotide position 415, causing the threonine (T) at amino acid position 139 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Pathogenic	0.29	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.6	D;.;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.023	D;.;.
Sift4G	Uncertain	0.027	D;.;.
Vest4		0.31
MutPred		0.60		Loss of sheet (P = 0.0357);.;.;
MVP		0.24
ClinPred		0.97	D
GERP RS		2.3
Varity_R		0.42
gMVP		0.35

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: rs1456896007; hg19: chr11-1769019;