12-13061736-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020853.2(FAM234B):c.694A>T(p.Met232Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM234B NM_020853.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.588

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05908391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM234B	NM_020853.2	c.694A>T	p.Met232Leu	missense_variant	4/13	ENST00000197268.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM234B	ENST00000197268.13	c.694A>T	p.Met232Leu	missense_variant	4/13	1	NM_020853.2	P1
FAM234B	ENST00000537625.1	c.22A>T	p.Met8Leu	missense_variant	1/9	1
FAM234B	ENST00000416494.6	c.694A>T	p.Met232Leu	missense_variant, NMD_transcript_variant	4/14	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.694A>T (p.M232L) alteration is located in exon 4 (coding exon 4) of the FAM234B gene. This alteration results from a A to T substitution at nucleotide position 694, causing the methionine (M) at amino acid position 232 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.6
Dann	Benign	0.61
DEOGEN2	Benign	0.0030	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.46	N
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.86	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.048
Sift	Benign	0.91	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.15
MutPred		0.52		Loss of ubiquitination at K231 (P = 0.1264);.;
MVP		0.092
MPC		0.12
ClinPred		0.064	T
GERP RS		1.9
Varity_R		0.063
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-13214670;