3-194633178-T-G

Variant names:

• chr3-194633178-T-G
• rs998707142
• NM_001011655.3:c.38A>C

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.38A>C​(p.Asp13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,534,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D13N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.245
• Publications: 0 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]

TMEM44-AS2 (HGNC:41082): (TMEM44 antisense RNA 2)

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=0.091228664).

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.38A>C	p.Asp13Ala	missense	Exon 1 of 10	NP_001011655.1	Q2T9K0-2
	TMEM44	NM_001166305.2		c.38A>C	p.Asp13Ala	missense	Exon 1 of 11	NP_001159777.1	Q2T9K0-1
	TMEM44	NM_138399.5		c.38A>C	p.Asp13Ala	missense	Exon 1 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.38A>C	p.Asp13Ala	missense	Exon 1 of 10	ENSP00000333355.6	Q2T9K0-2
	TMEM44	ENST00000392432.6	TSL:1	c.38A>C	p.Asp13Ala	missense	Exon 1 of 11	ENSP00000376227.2	Q2T9K0-1
	TMEM44	ENST00000473092.5	TSL:1	c.38A>C	p.Asp13Ala	missense	Exon 1 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151506 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000289 AC: 4 AN: 1383406 Hom.: 0 Cov.: 35 AF XY: 0.00000293 AC XY: 2 AN XY: 682388

African (AFR) AF: 0.0000676 AC: 2 AN: 29582

American (AMR) AF: 0.00 AC: 0 AN: 34948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24662

East Asian (EAS) AF: 0.00 AC: 0 AN: 33584

South Asian (SAS) AF: 0.00 AC: 0 AN: 78560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4412

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072748

Other (OTH) AF: 0.0000350 AC: 2 AN: 57220

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151506 Hom.: 0 Cov.: 33 AF XY: 0.0000676 AC XY: 5 AN XY: 73984

African (AFR) AF: 0.000121 AC: 5 AN: 41352

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10368

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67838

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.24
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.074
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.013	D
Polyphen		0.93	P
Vest4		0.20
MutPred		0.40		Loss of loop (P = 0.0031)
MVP		0.092
MPC		0.13
ClinPred		0.88	D
GERP RS		3.4
PromoterAI		0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.19
gMVP		0.13
Mutation Taster		=88/12	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: rs998707142; hg19: chr3-194353907;