chr7-19765857-C-T

Variant names:

• chr7-19765857-C-T
• rs6977660
• NM_001363562.2:c.147+6693G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363562.2(TMEM196):​c.147+6693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,876 control chromosomes in the GnomAD database, including 6,550 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6550 hom., cov: 32)
• Consequence: TMEM196 NM_001363562.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

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.147+6693G>A		intron	N/A	NP_001350491.1
	TMEM196	NM_001366625.1		c.165+6675G>A		intron	N/A	NP_001353554.1
	TMEM196	NM_001366626.1		c.165+6675G>A		intron	N/A	NP_001353555.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM196	ENST00000405844.6	TSL:5 MANE Select	c.147+6693G>A		intron	N/A	ENSP00000385087.2
	TMEM196	ENST00000405764.7	TSL:1	c.147+6693G>A		intron	N/A	ENSP00000384234.3
	TMEM196	ENST00000422233.5	TSL:5	c.-58+7710G>A		intron	N/A	ENSP00000414247.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38775 AN: 151758 Hom.: 6519 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38853 AN: 151876 Hom.: 6550 Cov.: 32 AF XY: 0.259 AC XY: 19242 AN XY: 74220

African (AFR) AF: 0.429 AC: 17746 AN: 41396

American (AMR) AF: 0.269 AC: 4097 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3105 AN: 5168

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4816

European-Finnish (FIN) AF: 0.131 AC: 1384 AN: 10528

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9757 AN: 67942

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.192 Hom.: 11543

Bravo AF: 0.276

Asia WGS AF: 0.407 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.19
DANN	Benign	0.38
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs6977660; hg19: chr7-19805480;