7-19772651-C-T

Variant names:

• chr7-19772651-C-T
• rs1429761233
• NM_001363562.2:c.46G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001363562.2(TMEM196):​c.46G>A​(p.Val16Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V16L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM196 NM_001363562.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50
• Publications: 0 publications found

Genes affected

TMEM196 (HGNC:22431): (transmembrane protein 196) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC107986774 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3326264).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363562.2. 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
	TMEM196	NM_001363562.2	MANE Select	c.46G>A	p.Val16Met	missense	Exon 1 of 5	NP_001350491.1	B7WNR7
	TMEM196	NM_001366625.1		c.46G>A	p.Val16Met	missense	Exon 1 of 5	NP_001353554.1
	TMEM196	NM_001366626.1		c.46G>A	p.Val16Met	missense	Exon 1 of 4	NP_001353555.1	Q5HYL7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM196	ENST00000405844.6	TSL:5 MANE Select	c.46G>A	p.Val16Met	missense	Exon 1 of 5	ENSP00000385087.2	B7WNR7
	TMEM196	ENST00000405764.7	TSL:1	c.46G>A	p.Val16Met	missense	Exon 1 of 4	ENSP00000384234.3	Q5HYL7-4
	TMEM196	ENST00000882494.1		c.46G>A	p.Val16Met	missense	Exon 1 of 3	ENSP00000552553.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1392010 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686456

African (AFR) AF: 0.00 AC: 0 AN: 31378

American (AMR) AF: 0.00 AC: 0 AN: 34998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25078

East Asian (EAS) AF: 0.00 AC: 0 AN: 35258

South Asian (SAS) AF: 0.00 AC: 0 AN: 78406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4056

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076032

Other (OTH) AF: 0.00 AC: 0 AN: 57588

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Pathogenic	1.0
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.42
MutPred		0.24		Loss of catalytic residue at V16 (P = 0.265)
MVP		0.21
MPC		0.037
ClinPred		0.93	D
GERP RS		6.0
gMVP		0.70
Mutation Taster		=80/20	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: rs1429761233; hg19: chr7-19812274;