12-119593946-T-C

Variant names:

• chr12-119593946-T-C
• NM_001136534.3:c.98T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001136534.3(TMEM233):​c.98T>C​(p.Met33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM233 NM_001136534.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49
• Publications: 0 publications found

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]

PRKAB1-AS1 (HGNC:58183):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023878217).
• BP6: Variant 12-119593946-T-C is Benign according to our data. Variant chr12-119593946-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2541416.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136534.3. 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
	TMEM233	NM_001136534.3	MANE Select	c.98T>C	p.Met33Thr	missense	Exon 1 of 3	NP_001130006.1	B4DJY2
	PRKAB1-AS1	NR_188489.1		n.787+236A>G		intron	N/A
	PRKAB1-AS1	NR_188490.1		n.186-40301A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM233	ENST00000426426.3	TSL:2 MANE Select	c.98T>C	p.Met33Thr	missense	Exon 1 of 3	ENSP00000403130.1	B4DJY2
	PRKAB1-AS1	ENST00000509470.2	TSL:1	n.320+236A>G		intron	N/A
	TMEM233	ENST00000971026.1		c.98T>C	p.Met33Thr	missense	Exon 1 of 4	ENSP00000641085.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399382 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690210

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078952

Other (OTH) AF: 0.00 AC: 0 AN: 58002

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.23
DANN	Benign	0.48
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.85	L
PhyloP100		-1.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.14
Sift	Benign	0.58	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.32		Gain of glycosylation at M33 (P = 0.0044)
MVP		0.20
ClinPred		0.052	T
GERP RS		-7.9
PromoterAI		-0.042	Neutral
Varity_R		0.047
gMVP		0.57
Mutation Taster		=93/7	polymorphism

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

hg19: chr12-120031751;