3-194633110-C-A

Position:

• chr3-194633110-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001011655.3(TMEM44):​c.106G>T​(p.Ala36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.18

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03823456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM44	NM_001011655.3	c.106G>T	p.Ala36Ser	missense_variant	1/10	ENST00000347147.9	NP_001011655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM44	ENST00000347147.9	c.106G>T	p.Ala36Ser	missense_variant	1/10	1	NM_001011655.3	ENSP00000333355.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398264 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 689802

Gnomad4 AFR exome AF: 0.0000317

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.106G>T (p.A36S) alteration is located in exon 1 (coding exon 1) of the TMEM44 gene. This alteration results from a G to T substitution at nucleotide position 106, causing the alanine (A) at amino acid position 36 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.00042	T;.;.;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.038	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.11	N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.10	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.41	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.15	B;B;B;.
Vest4		0.25
MutPred		0.31		Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP		0.014
MPC		0.11
ClinPred		0.86	D
GERP RS		-0.50
Varity_R		0.087
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-194353839;