7-19751353-T-C

Variant names:

• chr7-19751353-T-C
• rs9332392
• NM_001363562.2:c.147+21197A>G

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+21197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,078 control chromosomes in the GnomAD database, including 23,078 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 0.50 (23078 hom., cov: 32)
• Consequence: TMEM196 NM_001363562.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM196	NM_001363562.2	c.147+21197A>G		intron_variant	Intron 1 of 4	ENST00000405844.6	NP_001350491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM196	ENST00000405844.6	c.147+21197A>G		intron_variant	Intron 1 of 4	5	NM_001363562.2	ENSP00000385087.2
TMEM196	ENST00000405764.7	c.147+21197A>G		intron_variant	Intron 1 of 3	1		ENSP00000384234.3
TMEM196	ENST00000422233.5	c.-57-21915A>G		intron_variant	Intron 1 of 4	5		ENSP00000414247.1
TMEM196	ENST00000493519.2	c.-58+21749A>G		intron_variant	Intron 1 of 3	5		ENSP00000438368.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75357 AN: 151960 Hom.: 23030 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.496 AC: 75455 AN: 152078 Hom.: 23078 Cov.: 32 AF XY: 0.501 AC XY: 37219 AN XY: 74310

African (AFR) AF: 0.820 AC: 34014 AN: 41496

American (AMR) AF: 0.469 AC: 7155 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3464

East Asian (EAS) AF: 0.970 AC: 5015 AN: 5172

South Asian (SAS) AF: 0.581 AC: 2797 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3148 AN: 10574

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20722 AN: 67968

Other (OTH) AF: 0.465 AC: 983 AN: 2114

Alfa AF: 0.417 Hom.: 6868

Bravo AF: 0.525

Asia WGS AF: 0.741 AC: 2575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.0
DANN	Benign	0.43
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9332392; hg19: chr7-19790976;