rs151289436

Variant names:

• chr17-75486316-C-G
• rs151289436
• NM_014738.6:c.299C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-75486316-C-G
• chr17-75486316-C-T

Variant summary

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

The NM_014738.6(TMEM94):​c.299C>G​(p.Ser100Trp) 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 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. S100L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TMEM94 NM_014738.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00700
• Publications: 0 publications found

Genes affected

TMEM94 (HGNC:28983): (transmembrane protein 94) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM94 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with cardiac defects and dysmorphic facies

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, ClinGen, Ambry Genetics

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=0.19575322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014738.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM94	NM_014738.6	MANE Select	c.299C>G	p.Ser100Trp	missense	Exon 5 of 32	NP_055553.3
	TMEM94	NM_001438842.1		c.299C>G	p.Ser100Trp	missense	Exon 5 of 32	NP_001425771.1
	TMEM94	NM_001438843.1		c.329C>G	p.Ser110Trp	missense	Exon 4 of 31	NP_001425772.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM94	ENST00000314256.12	TSL:1 MANE Select	c.299C>G	p.Ser100Trp	missense	Exon 5 of 32	ENSP00000313885.7	Q12767-1
	TMEM94	ENST00000956011.1		c.299C>G	p.Ser100Trp	missense	Exon 5 of 32	ENSP00000626070.1
	TMEM94	ENST00000861539.1		c.299C>G	p.Ser100Trp	missense	Exon 5 of 32	ENSP00000531598.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	13
DANN	Benign	0.46
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.058	N
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.49	T
PhyloP100		-0.0070
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.26	N
REVEL	Uncertain	0.48
Sift	Benign	0.18	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.89	P
Vest4		0.53
MutPred		0.40		Loss of disorder (P = 0.1053)
MVP		0.65
MPC		0.92
ClinPred		0.21	T
GERP RS		2.2
Varity_R		0.033
gMVP		0.69
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs151289436; hg19: chr17-73482397;