Variant chr6-34246807-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008703.4(SMIM29):c.305C>T(p.Thr102Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,612,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

SMIM29
NM_001008703.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

Variant links:

Genes affected

SMIM29 (HGNC:1340): (small integral membrane protein 29) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14393505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM29	NM_001008703.4 linkuse as main transcript	c.305C>T	p.Thr102Met	missense_variant	5/5	ENST00000476320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM29	ENST00000476320.6 linkuse as main transcript	c.305C>T	p.Thr102Met	missense_variant	5/5	2	NM_001008703.4	P1	Q86T20-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000105

AC:

AN:

248276

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1460604

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000115

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000118

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000404

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.187C>T (p.R63C) alteration is located in exon 5 (coding exon 3) of the C6orf1 gene. This alteration results from a C to T substitution at nucleotide position 187, causing the arginine (R) at amino acid position 63 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.55

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D;D;D;D;D

ClinPred

0.22

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.018

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over