rs773061292

Variant names:

• chr12-111931740-G-A
• rs773061292
• NM_001193531.2:c.895C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-111931740-G-A
• chr12-111931740-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001193531.2(TMEM116):​c.895C>T​(p.Arg299Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,288 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R299Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: TMEM116 NM_001193531.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00
• Publications: 0 publications found

Genes affected

TMEM116 (HGNC:25084): (transmembrane protein 116) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21442726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM116	NM_001193531.2	c.895C>T	p.Arg299Trp	missense_variant	Exon 11 of 11	ENST00000552374.7	NP_001180460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM116	ENST00000552374.7	c.895C>T	p.Arg299Trp	missense_variant	Exon 11 of 11	1	NM_001193531.2	ENSP00000447731.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152054 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000806 AC: 2 AN: 248252 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1459234 Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15 AN XY: 725816

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85728

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1110798

Other (OTH) AF: 0.0000498 AC: 3 AN: 60272

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152054 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.895C>T (p.R299W) alteration is located in exon 11 (coding exon 10) of the TMEM116 gene. This alteration results from a C to T substitution at nucleotide position 895, causing the arginine (R) at amino acid position 299 to be replaced by a tryptophan (W). 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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T;.;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PhyloP100		3.0
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.16	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.99	D;.;.;D
Vest4		0.26
MutPred		0.30		Loss of disorder (P = 0.0179);.;.;.;
MVP		0.28
MPC		0.59
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.096
gMVP		0.38
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs773061292; hg19: chr12-112369544;