chr3-194617217-G-T

Position:

• chr3-194617217-G-T

Variant summary

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

The ENST00000347147.9(TMEM44):​c.665C>A​(p.Ala222Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM44 ENST00000347147.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

Genes affected

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

TMEM44 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM44	NM_001011655.3	c.665C>A	p.Ala222Asp	missense_variant	6/10	ENST00000347147.9	NP_001011655.1
TMEM44	NM_001166305.2	c.806C>A	p.Ala269Asp	missense_variant	7/11		NP_001159777.1
TMEM44	NM_138399.5	c.665C>A	p.Ala222Asp	missense_variant	6/11		NP_612408.3
TMEM44	NM_001166306.2	c.665C>A	p.Ala222Asp	missense_variant	6/10		NP_001159778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM44	ENST00000347147.9	c.665C>A	p.Ala222Asp	missense_variant	6/10	1	NM_001011655.3	ENSP00000333355.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 61

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 15, 2024

The c.806C>A (p.A269D) alteration is located in exon 7 (coding exon 7) of the TMEM44 gene. This alteration results from a C to A substitution at nucleotide position 806, causing the alanine (A) at amino acid position 269 to be replaced by an aspartic acid (D). 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M;.;.;.
MutationTaster	Benign	0.97	D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.99	D;D;D;.
Vest4		0.80
MutPred		0.52		Loss of MoRF binding (P = 0.0713);.;.;.;
MVP		0.10
MPC		0.21
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.65
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-194337946;