rs1422451724

Variant names:

• chr3-194604431-G-A
• rs1422451724
• ENST00000381975.7:c.1028C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001166306.2(TMEM44):​c.1028C>T​(p.Pro343Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,368,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TMEM44 NM_001166306.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.615
• 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]

LOC105374291 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084091604).
• BP6: Variant 3-194604431-G-A is Benign according to our data. Variant chr3-194604431-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3458433.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166306.2. 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.1032C>T	p.Ala344Ala	synonymous	Exon 9 of 10	NP_001011655.1	Q2T9K0-2
	TMEM44	NM_001166306.2		c.1028C>T	p.Pro343Leu	missense	Exon 9 of 10	NP_001159778.1	Q2T9K0-4
	TMEM44	NM_001166305.2		c.1173C>T	p.Ala391Ala	synonymous	Exon 10 of 11	NP_001159777.1	Q2T9K0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM44	ENST00000381975.7	TSL:1	c.1028C>T	p.Pro343Leu	missense	Exon 9 of 10	ENSP00000371402.3	Q2T9K0-4
	TMEM44	ENST00000429560.1	TSL:1	c.224C>T	p.Pro75Leu	missense	Exon 3 of 4	ENSP00000403053.1	Q6PL43
	TMEM44	ENST00000347147.9	TSL:1 MANE Select	c.1032C>T	p.Ala344Ala	synonymous	Exon 9 of 10	ENSP00000333355.6	Q2T9K0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000730 AC: 1 AN: 137010 AF XY: 0.0000139

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000192

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1368352 Hom.: 0 Cov.: 33 AF XY: 0.00000149 AC XY: 1 AN XY: 670146

African (AFR) AF: 0.00 AC: 0 AN: 30986

American (AMR) AF: 0.00 AC: 0 AN: 32952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23620

East Asian (EAS) AF: 0.00 AC: 0 AN: 35092

South Asian (SAS) AF: 0.00 AC: 0 AN: 76132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058958

Other (OTH) AF: 0.00 AC: 0 AN: 56558

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.11
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.2
DANN	Uncertain	0.99
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.61
PROVEAN	Benign	0.21	N
REVEL	Benign	0.0080
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.030	D
Polyphen		0.053	B
Vest4		0.31
MutPred		0.34		Loss of catalytic residue at P75 (P = 0.0342)
MVP		0.20
ClinPred		0.18	T
GERP RS		2.2
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1422451724; hg19: chr3-194325160;