dbSNP rs770280178: FAM234A:p.Thr147Lys (chr16-260023-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032039.4(FAM234A):c.440C>A(p.Thr147Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. T147M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

FAM234A
NM_032039.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.742

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:

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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=0.07711062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM234A	NM_032039.4 link	c.440C>A	p.Thr147Lys	missense_variant	Exon 5 of 13	ENST00000399932.8	NP_114428.1	Q9H0X4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM234A	ENST00000399932.8 link	c.440C>A	p.Thr147Lys	missense_variant	Exon 5 of 13	1	NM_032039.4	ENSP00000382814.3		Q9H0X4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248912

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135172

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.061

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

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.66

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

M_CAP

Benign

0.030

MetaRNN

Benign

0.077

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

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.1

N;N;N;N;N;N;.

REVEL

Benign

0.21

Sift

Benign

0.33

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

Sift4G

Uncertain

0.044

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

Polyphen

0.68

P;P;.;.;.;P;.

Vest4

0.42

MutPred

0.37

Gain of ubiquitination at T147 (P = 0.0121);Gain of ubiquitination at T147 (P = 0.0121);Gain of ubiquitination at T147 (P = 0.0121);.;Gain of ubiquitination at T147 (P = 0.0121);Gain of ubiquitination at T147 (P = 0.0121);Gain of ubiquitination at T147 (P = 0.0121);

MVP

0.30

MPC

0.22

ClinPred

0.14

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.047

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over