chr3-185496917-G-C

Variant names:

• chr3-185496917-G-C
• rs372298444
• NM_080652.4:c.184C>G

Variant summary

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

The NM_080652.4(TMEM41A):​c.184C>G​(p.Arg62Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R62Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM41A NM_080652.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

TMEM41A (HGNC:30544): (transmembrane protein 41A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17407385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080652.4. 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
	TMEM41A	NM_080652.4	MANE Select	c.184C>G	p.Arg62Gly	missense	Exon 2 of 5	NP_542383.1	Q96HV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM41A	ENST00000421852.6	TSL:1 MANE Select	c.184C>G	p.Arg62Gly	missense	Exon 2 of 5	ENSP00000406885.1	Q96HV5
	TMEM41A	ENST00000856958.1		c.184C>G	p.Arg62Gly	missense	Exon 2 of 4	ENSP00000527017.1
	TMEM41A	ENST00000296254.3	TSL:2	c.184C>G	p.Arg62Gly	missense	Exon 2 of 3	ENSP00000296254.3	H7BXL1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451476 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720870

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 42638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25728

East Asian (EAS) AF: 0.00 AC: 0 AN: 39362

South Asian (SAS) AF: 0.00 AC: 0 AN: 83704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108440

Other (OTH) AF: 0.00 AC: 0 AN: 60092

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.056
Sift	Uncertain	0.024	D
Sift4G	Benign	0.11	T
Polyphen		0.30	B
Vest4		0.36
MutPred		0.45		Loss of ubiquitination at K63 (P = 0.0702)
MVP		0.076
MPC		0.26
ClinPred		0.95	D
GERP RS		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.53
Mutation Taster		=77/23	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: rs372298444; hg19: chr3-185214705;