chr3-194604358-C-A

Variant names:

• chr3-194604358-C-A
• rs142364954
• NM_001011655.3:c.1105G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001011655.3(TMEM44):​c.1105G>T​(p.Val369Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,567,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. V369I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10417342).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011655.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM44	NM_001011655.3	MANE Select	c.1105G>T	p.Val369Phe	missense	Exon 9 of 10	NP_001011655.1	Q2T9K0-2
	TMEM44	NM_001166305.2		c.1246G>T	p.Val416Phe	missense	Exon 10 of 11	NP_001159777.1	Q2T9K0-1
	TMEM44	NM_138399.5		c.1105G>T	p.Val369Phe	missense	Exon 9 of 11	NP_612408.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM44	ENST00000347147.9	TSL:1 MANE Select	c.1105G>T	p.Val369Phe	missense	Exon 9 of 10	ENSP00000333355.6	Q2T9K0-2
	TMEM44	ENST00000392432.6	TSL:1	c.1246G>T	p.Val416Phe	missense	Exon 10 of 11	ENSP00000376227.2	Q2T9K0-1
	TMEM44	ENST00000473092.5	TSL:1	c.1105G>T	p.Val369Phe	missense	Exon 9 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1415648 Hom.: 0 Cov.: 33 AF XY: 0.00000143 AC XY: 1 AN XY: 699974

African (AFR) AF: 0.00 AC: 0 AN: 32264

American (AMR) AF: 0.00 AC: 0 AN: 37780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25310

East Asian (EAS) AF: 0.00 AC: 0 AN: 36786

South Asian (SAS) AF: 0.00 AC: 0 AN: 80352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088598

Other (OTH) AF: 0.00 AC: 0 AN: 58630

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.097
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.97	D
Vest4		0.35
MutPred		0.13		Gain of glycosylation at Y413 (P = 0.0093)
MVP		0.048
MPC		0.026
ClinPred		0.76	D
GERP RS		0.15
Varity_R		0.17
gMVP		0.35
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs142364954; hg19: chr3-194325087;