3-194633134-T-C

Variant names:

• chr3-194633134-T-C
• rs1177286175
• NM_001011655.3:c.82A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001011655.3(TMEM44):​c.82A>G​(p.Ile28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000432 in 1,551,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

Genes affected

TMEM44 (HGNC:25120): (transmembrane protein 44) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM44-AS2 (HGNC:41082): (TMEM44 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07947761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM44	NM_001011655.3	c.82A>G	p.Ile28Val	missense_variant	Exon 1 of 10	ENST00000347147.9	NP_001011655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM44	ENST00000347147.9	c.82A>G	p.Ile28Val	missense_variant	Exon 1 of 10	1	NM_001011655.3	ENSP00000333355.6

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152022 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000131 AC: 2 AN: 152982 Hom.: 0 AF XY: 0.0000123 AC XY: 1 AN XY: 81202

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000464 AC: 65 AN: 1399484 Hom.: 0 Cov.: 42 AF XY: 0.0000463 AC XY: 32 AN XY: 690530

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000592

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152022 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74254

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0027	T;.;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.61	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.079	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.070	N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.23	T;T;T;T
Sift4G	Pathogenic	0.0	D;D;T;T
Polyphen		0.88	P;B;P;.
Vest4		0.15
MutPred		0.21		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.040
MPC		0.025
ClinPred		0.11	T
GERP RS		-0.35
Varity_R		0.058
gMVP		0.068

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: rs1177286175; hg19: chr3-194353863;