Genetic Variant FAM234B:p.Asp36Glu (chr12-13055621-T-G) – 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_020853.2(FAM234B):c.108T>G(p.Asp36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,858 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: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

FAM234B
NM_020853.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.711

Variant links:

Genes affected

FAM234B (HGNC:29288): (family with sequence similarity 234 member B) Predicted to be located in Golgi apparatus and cytoskeleton. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM234B 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=0.1343607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM234B	NM_020853.2 link	c.108T>G	p.Asp36Glu	missense_variant	Exon 2 of 13	ENST00000197268.13	NP_065904.1	A2RU67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM234B	ENST00000197268.13 link	c.108T>G	p.Asp36Glu	missense_variant	Exon 2 of 13	1	NM_020853.2	ENSP00000197268.8		A2RU67
FAM234B	ENST00000416494.6 link	n.108T>G		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000394063.2		A2RU67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251384

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135864

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:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.108T>G (p.D36E) alteration is located in exon 2 (coding exon 2) of the FAM234B gene. This alteration results from a T to G substitution at nucleotide position 108, causing the aspartic acid (D) at amino acid position 36 to be replaced by a glutamic acid (E). 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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.39

CADD

Benign

8.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.36

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.1

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.30

MutPred

0.39

Gain of helix (P = 0.0425);

MVP

0.072

MPC

0.14

ClinPred

0.29

GERP RS

-4.1

Varity_R

0.36

gMVP

0.20

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