chr10-17771268-T-G

Position:

• chr10-17771268-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001098844.3(TMEM236):​c.258-41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,579,420 control chromosomes in the GnomAD database, including 2,167 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 0.042 (262 hom., cov: 33)
  • Exomes 𝑓: 0.031 (1905 hom.)
• Consequence: TMEM236 NM_001098844.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

TMEM236 (HGNC:23473): (transmembrane protein 236) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM236	NM_001098844.3	c.258-41T>G		intron_variant		ENST00000377495.2	NP_001092314.1
TMEM236	XM_017016574.2	c.72-41T>G		intron_variant			XP_016872063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM236	ENST00000377495.2	c.258-41T>G		intron_variant		2	NM_001098844.3	ENSP00000366715	P1

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6347 AN: 152202 Hom.: 264 Cov.: 33

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0401

GnomAD3 exomes AF: 0.0619 AC: 9806 AN: 158416 Hom.: 825 AF XY: 0.0622 AC XY: 5342 AN XY: 85858

Gnomad AFR exome AF: 0.0525

Gnomad AMR exome AF: 0.0620

Gnomad ASJ exome AF: 0.0876

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.0236

Gnomad OTH exome AF: 0.0484

GnomAD4 exome AF: 0.0311 AC: 44336 AN: 1427100 Hom.: 1905 Cov.: 25 AF XY: 0.0331 AC XY: 23575 AN XY: 712580

Gnomad4 AFR exome AF: 0.0506

Gnomad4 AMR exome AF: 0.0551

Gnomad4 ASJ exome AF: 0.0805

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0152

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0422

GnomAD4 genome AF: 0.0417 AC: 6349 AN: 152320 Hom.: 262 Cov.: 33 AF XY: 0.0444 AC XY: 3311 AN XY: 74490

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0392

Alfa AF: 0.0387 Hom.: 102

Bravo AF: 0.0434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs10508546; hg19: chr10-17813267; COSMIC: COSV57738048;