chr12-119598430-G-A

Position:

• chr12-119598430-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136534.3(TMEM233):​c.186+4396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,070 control chromosomes in the GnomAD database, including 9,452 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 0.34 (9452 hom., cov: 32)
• Consequence: TMEM233 NM_001136534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

Genes affected

TMEM233 (HGNC:37219): (transmembrane protein 233) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM233	NM_001136534.3	c.186+4396G>A		intron_variant		ENST00000426426.3	NP_001130006.1
LOC105370027	XR_007063484.1	n.65-44785C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM233	ENST00000426426.3	c.186+4396G>A		intron_variant		2	NM_001136534.3	ENSP00000403130	P1
	ENST00000537366.5	n.138-44785C>T		intron_variant, non_coding_transcript_variant		3
TMEM233	ENST00000453450.2	n.121+4396G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51974 AN: 151952 Hom.: 9446 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.342 AC: 52000 AN: 152070 Hom.: 9452 Cov.: 32 AF XY: 0.335 AC XY: 24868 AN XY: 74312

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.339

Alfa AF: 0.345 Hom.: 1634

Bravo AF: 0.338

Asia WGS AF: 0.156 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.28

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: rs7312321; hg19: chr12-120036235;