chr11-1747811-C-A

Position:

• chr11-1747811-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170820.4(IFITM10):​c.393G>T​(p.Lys131Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,398,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: IFITM10 NM_001170820.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19546452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFITM10	NM_001170820.4	c.393G>T	p.Lys131Asn	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.393G>T	p.Lys131Asn	missense_variant	2/3	3	NM_001170820.4	ENSP00000344430.4
ENSG00000250644	ENST00000636615.1	c.1380G>T	p.Lys460Asn	missense_variant	9/10	5		ENSP00000490014.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1398190 Hom.: 0 Cov.: 31 AF XY: 0.00000435 AC XY: 3 AN XY: 689498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 27, 2022

The c.393G>T (p.K131N) alteration is located in exon 2 (coding exon 2) of the IFITM10 gene. This alteration results from a G to T substitution at nucleotide position 393, causing the lysine (K) at amino acid position 131 to be replaced by an asparagine (N). 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.091
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.1	N;.;.
REVEL	Benign	0.028
Sift	Benign	0.045	D;.;.
Sift4G	Uncertain	0.039	D;.;.
Vest4		0.38
MutPred		0.33		Loss of methylation at K131 (P = 0.003);.;.;
MVP		0.16
ClinPred		0.87	D
GERP RS		2.6
Varity_R		0.33
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-1769041;