chr3-194604391-C-G

Variant names:

• chr3-194604391-C-G
• rs369571041
• NM_001011655.3:c.1072G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001011655.3(TMEM44):​c.1072G>C​(p.Ala358Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00049 in 1,547,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.81
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034315705).

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.1072G>C	p.Ala358Pro	missense	Exon 9 of 10	NP_001011655.1	Q2T9K0-2
	TMEM44	NM_001166305.2		c.1213G>C	p.Ala405Pro	missense	Exon 10 of 11	NP_001159777.1	Q2T9K0-1
	TMEM44	NM_138399.5		c.1072G>C	p.Ala358Pro	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.1072G>C	p.Ala358Pro	missense	Exon 9 of 10	ENSP00000333355.6	Q2T9K0-2
	TMEM44	ENST00000392432.6	TSL:1	c.1213G>C	p.Ala405Pro	missense	Exon 10 of 11	ENSP00000376227.2	Q2T9K0-1
	TMEM44	ENST00000473092.5	TSL:1	c.1072G>C	p.Ala358Pro	missense	Exon 9 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000296 AC: 46 AN: 155472 AF XY: 0.000267

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000652

Gnomad NFE exome AF: 0.000708

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.000515 AC: 719 AN: 1395504 Hom.: 0 Cov.: 33 AF XY: 0.000503 AC XY: 346 AN XY: 687602

African (AFR) AF: 0.0000317 AC: 1 AN: 31594

American (AMR) AF: 0.0000283 AC: 1 AN: 35384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24940

East Asian (EAS) AF: 0.00 AC: 0 AN: 35712

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79074

European-Finnish (FIN) AF: 0.000122 AC: 6 AN: 49218

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5662

European-Non Finnish (NFE) AF: 0.000641 AC: 690 AN: 1076110

Other (OTH) AF: 0.000311 AC: 18 AN: 57810

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152366 Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17 AN XY: 74512

African (AFR) AF: 0.0000481 AC: 2 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000591 Hom.: 0

Bravo AF: 0.000189

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000235 AC: 2

ExAC AF: 0.0000899 AC: 10

ClinVar

ClinVar submissions

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	Benign	0.17
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.012
DANN	Benign	0.96
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.8
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.043	D
Sift4G	Uncertain	0.028	D
Polyphen		0.61	P
Vest4		0.086
MVP		0.014
MPC		0.16
ClinPred		0.040	T
GERP RS		-6.5
Varity_R		0.080
gMVP		0.18
Mutation Taster		=95/5	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: rs369571041; hg19: chr3-194325120;