3-194604372-G-T

Variant names:

• chr3-194604372-G-T
• rs151243596
• NM_001011655.3:c.1091C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001011655.3(TMEM44):​c.1091C>A​(p.Pro364Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000711 in 1,407,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P364L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.88
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27526706).

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.1091C>A	p.Pro364Gln	missense	Exon 9 of 10	NP_001011655.1	Q2T9K0-2
	TMEM44	NM_001166305.2		c.1232C>A	p.Pro411Gln	missense	Exon 10 of 11	NP_001159777.1	Q2T9K0-1
	TMEM44	NM_138399.5		c.1091C>A	p.Pro364Gln	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.1091C>A	p.Pro364Gln	missense	Exon 9 of 10	ENSP00000333355.6	Q2T9K0-2
	TMEM44	ENST00000392432.6	TSL:1	c.1232C>A	p.Pro411Gln	missense	Exon 10 of 11	ENSP00000376227.2	Q2T9K0-1
	TMEM44	ENST00000473092.5	TSL:1	c.1091C>A	p.Pro364Gln	missense	Exon 9 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1407052 Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1 AN XY: 694994

African (AFR) AF: 0.00 AC: 0 AN: 31962

American (AMR) AF: 0.00 AC: 0 AN: 36638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25152

East Asian (EAS) AF: 0.00 AC: 0 AN: 36228

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083540

Other (OTH) AF: 0.00 AC: 0 AN: 58330

GnomAD4 genome Cov.: 33

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	0.28
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.31		Gain of glycosylation at Y413 (P = 0.0093)
MVP		0.061
MPC		0.034
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.64
gMVP		0.44
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs151243596; hg19: chr3-194325101;