chr11-1735351-T-C

Position:

• chr11-1735351-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001170820.4(IFITM10):​c.616A>G​(p.Ser206Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IFITM10 NM_001170820.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFITM10	NM_001170820.4	c.616A>G	p.Ser206Gly	missense_variant	3/3	ENST00000340134.5	NP_001164291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFITM10	ENST00000340134.5	c.616A>G	p.Ser206Gly	missense_variant	3/3	3	NM_001170820.4	ENSP00000344430.4
ENSG00000250644	ENST00000636615.1	c.1603A>G	p.Ser535Gly	missense_variant	10/10	5		ENSP00000490014.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399400 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Feb 23, 2023

The c.616A>G (p.S206G) alteration is located in exon 3 (coding exon 3) of the IFITM10 gene. This alteration results from a A to G substitution at nucleotide position 616, causing the serine (S) at amino acid position 206 to be replaced by a glycine (G). 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	0.80
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;.;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N;.;.
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.053	T;.;.
Vest4		0.65
MutPred		0.69		Gain of catalytic residue at I204 (P = 0.1716);.;.;
MVP		0.55
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.39
gMVP		0.82

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: chr11-1756581;