7-19722098-G-C

Variant names:

• chr7-19722098-G-C
• rs754639455
• ENST00000405764.7:c.496C>G

Variant summary

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

The NM_001366626.1(TMEM196):​c.514C>G​(p.Leu172Val) 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. L172M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM196 NM_001366626.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366626.1. 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.*30C>G		3_prime_UTR	Exon 5 of 5	NP_001350491.1	B7WNR7
	TMEM196	NM_001366626.1		c.514C>G	p.Leu172Val	missense	Exon 4 of 4	NP_001353555.1	Q5HYL7-1
	TMEM196	NM_152774.3		c.496C>G	p.Leu166Val	missense	Exon 4 of 4	NP_689987.3	Q5HYL7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM196	ENST00000405764.7	TSL:1	c.496C>G	p.Leu166Val	missense	Exon 4 of 4	ENSP00000384234.3	Q5HYL7-4
	TMEM196	ENST00000405844.6	TSL:5 MANE Select	c.*30C>G		3_prime_UTR	Exon 5 of 5	ENSP00000385087.2	B7WNR7
	TMEM196	ENST00000493519.2	TSL:5	c.292C>G	p.Leu98Val	missense	Exon 4 of 4	ENSP00000438368.1	Q5HYL7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	8.4
DANN	Uncertain	1.0
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.88	T
PhyloP100		3.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.16
Sift	Benign	0.18	T
Sift4G	Benign	0.61	T
Polyphen		0.59	P
Vest4		0.35
MVP		0.13
MPC		0.023
ClinPred		0.47	T
GERP RS		5.8
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: 36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754639455; hg19: chr7-19761721;