3-194604303-A-G

Position:

• chr3-194604303-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001011655.3(TMEM44):​c.1160T>C​(p.Ile387Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,429,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

Genes affected

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

LOC105374291 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35584188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM44	NM_001011655.3	c.1160T>C	p.Ile387Thr	missense_variant	9/10	ENST00000347147.9	NP_001011655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM44	ENST00000347147.9	c.1160T>C	p.Ile387Thr	missense_variant	9/10	1	NM_001011655.3	ENSP00000333355.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1429306 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 708138

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: 0.0000123

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

Jul 09, 2021

The c.1301T>C (p.I434T) alteration is located in exon 10 (coding exon 10) of the TMEM44 gene. This alteration results from a T to C substitution at nucleotide position 1301, causing the isoleucine (I) at amino acid position 434 to be replaced by a threonine (T). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;T;.;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.76	T;T;T;T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Benign	-0.59	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N;D;N;N;D
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;T;T;D
Polyphen		0.76	P;.;P;.;.
Vest4		0.38
MutPred		0.30		Gain of glycosylation at S436 (P = 0.0072);.;.;.;.;
MVP		0.24
MPC		0.050
ClinPred		0.93	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.16

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: chr3-194325032;