Variant 16-260019-A-T 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_032039.4(FAM234A):c.436A>T(p.Ser146Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,660 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

FAM234A
NM_032039.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

Variant links:

Genes affected

FAM234A (HGNC:14163): (family with sequence similarity 234 member A) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

FAM234A 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=0.23288995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM234A	NM_032039.4 linkuse as main transcript	c.436A>T	p.Ser146Cys	missense_variant	5/13	ENST00000399932.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM234A	ENST00000399932.8 linkuse as main transcript	c.436A>T	p.Ser146Cys	missense_variant	5/13	1	NM_032039.4	P1	Q9H0X4-1

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

117

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000237

AC:

AN:

248830

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000373

Gnomad NFE exome

AF:

0.000364

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.00122

AC:

1787

AN:

1461306

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

845

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.00144

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152354

Hom.:

Cov.:

AF XY:

0.000805

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000658

Hom.:

Bravo

AF:

0.000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000245

AC:

ESP6500EA

AF:

0.000359

AC:

ExAC

AF:

0.000364

AC:

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

Dec 19, 2023

The c.436A>T (p.S146C) alteration is located in exon 5 (coding exon 3) of the FAM234A gene. This alteration results from a A to T substitution at nucleotide position 436, causing the serine (S) at amino acid position 146 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;.;.;.;.;T;.

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.032

MetaRNN

Benign

0.23

T;T;T;T;T;T;T

MetaSVM

Benign

-0.44

MutationTaster

Benign

0.56

N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.8

D;D;D;D;D;D;.

REVEL

Benign

0.23

Sift

Uncertain

0.0040

D;D;D;D;D;D;.

Sift4G

Uncertain

0.016

D;D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;.;D;.

Vest4

0.53

MVP

0.79

MPC

0.57

ClinPred

0.13

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.70

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