10-17771268-T-G

Variant names:

• chr10-17771268-T-G
• rs10508546
• NM_001098844.3:c.258-41T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM236	NM_001098844.3	c.258-41T>G		intron_variant	Intron 1 of 3	ENST00000377495.2	NP_001092314.1
TMEM236	XM_017016574.2	c.72-41T>G		intron_variant	Intron 1 of 3		XP_016872063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM236	ENST00000377495.2	c.258-41T>G		intron_variant	Intron 1 of 3	2	NM_001098844.3	ENSP00000366715.1

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

GnomAD2 exomes AF: 0.0619 AC: 9806 AN: 158416 AF XY: 0.0622

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 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

African (AFR) AF: 0.0506 AC: 1654 AN: 32682

American (AMR) AF: 0.0551 AC: 2462 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.0805 AC: 2086 AN: 25916

East Asian (EAS) AF: 0.209 AC: 8267 AN: 39498

South Asian (SAS) AF: 0.103 AC: 8849 AN: 85514

European-Finnish (FIN) AF: 0.0152 AC: 809 AN: 53386

Middle Eastern (MID) AF: 0.0543 AC: 310 AN: 5714

European-Non Finnish (NFE) AF: 0.0161 AC: 17401 AN: 1080508

Other (OTH) AF: 0.0422 AC: 2498 AN: 59232

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

African (AFR) AF: 0.0494 AC: 2052 AN: 41570

American (AMR) AF: 0.0523 AC: 800 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1084 AN: 5180

South Asian (SAS) AF: 0.119 AC: 574 AN: 4826

European-Finnish (FIN) AF: 0.0125 AC: 133 AN: 10622

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0187 AC: 1272 AN: 68030

Other (OTH) AF: 0.0392 AC: 83 AN: 2116

Alfa AF: 0.0402 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
PhyloP100		0.17
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: rs10508546; hg19: chr10-17813267; COSMIC: COSV57738048;