chr6-129833561-G-T

Variant names:

• chr6-129833561-G-T
• rs146090235
• NM_001010876.2:c.218C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010876.2(TMEM244):​c.218C>A​(p.Thr73Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,136 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T73I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM244 NM_001010876.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

Genes affected

TMEM244 (HGNC:21571): (transmembrane protein 244) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM244	NM_001010876.2	c.218C>A	p.Thr73Asn	missense_variant	Exon 4 of 5	ENST00000368143.6	NP_001010876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM244	ENST00000368143.6	c.218C>A	p.Thr73Asn	missense_variant	Exon 4 of 5	2	NM_001010876.2	ENSP00000357125.1
TMEM244	ENST00000438392.3	c.218C>A	p.Thr73Asn	missense_variant	Exon 5 of 6	5		ENSP00000403755.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460136 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726404

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 85994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111244

Other (OTH) AF: 0.0000166 AC: 1 AN: 60314

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.0080	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		3.5
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.99	D;D
Vest4		0.69
MutPred		0.42		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.57
MPC		0.073
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.62
gMVP		0.68
Mutation Taster		=83/17	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

dbSNP: rs146090235; hg19: chr6-130154706;