Variant 12-13044438-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020853.2(FAM234B):c.35C>G(p.Pro12Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000357 in 1,399,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

FAM234B
NM_020853.2 missense, splice_region

Scores

Splicing: ADA: 0.3819

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33987463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM234B	NM_020853.2 linkuse as main transcript	c.35C>G	p.Pro12Arg	missense_variant, splice_region_variant	1/13	ENST00000197268.13	NP_065904.1	A2RU67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM234B	ENST00000197268.13 linkuse as main transcript	c.35C>G	p.Pro12Arg	missense_variant, splice_region_variant	1/13	1	NM_020853.2	ENSP00000197268.8		A2RU67
FAM234B	ENST00000416494.6 linkuse as main transcript	n.35C>G		splice_region_variant, non_coding_transcript_exon_variant	1/14	2		ENSP00000394063.2		A2RU67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000655

AC:

AN:

152760

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81236

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:

0.00

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399060

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690152

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

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

Aug 27, 2024

The c.35C>G (p.P12R) alteration is located in exon 1 (coding exon 1) of the FAM234B gene. This alteration results from a C to G substitution at nucleotide position 35, causing the proline (P) at amino acid position 12 to be replaced by an arginine (R). 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

0.85

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.68

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.93

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.8

REVEL

Benign

0.16

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.97

Vest4

0.42

MutPred

0.36

Gain of MoRF binding (P = 0.0108);

MVP

0.32

MPC

0.39

ClinPred

0.56

GERP RS

4.1

Varity_R

0.50

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.38

dbscSNV1_RF

Benign

0.48

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