16-254522-A-T

Variant names:

• chr16-254522-A-T
• NM_032039.4:c.109A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032039.4(FAM234A):​c.109A>T​(p.Ser37Cys) 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. 12/19 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: FAM234A NM_032039.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

Genes affected

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

ACMG classification

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=0.1211755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM234A	NM_032039.4	c.109A>T	p.Ser37Cys	missense_variant	Exon 3 of 13	ENST00000399932.8	NP_114428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM234A	ENST00000399932.8	c.109A>T	p.Ser37Cys	missense_variant	Exon 3 of 13	1	NM_032039.4	ENSP00000382814.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109A>T (p.S37C) alteration is located in exon 3 (coding exon 1) of the FAM234A gene. This alteration results from a A to T substitution at nucleotide position 109, causing the serine (S) at amino acid position 37 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	Benign	0.090
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T;.;.;.;.;.;.;.;.;T;.;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.66	.;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N;N;D;D;D;D;N;N;N;N;D;D;.
REVEL	Benign	0.043
Sift	Uncertain	0.025	D;D;D;D;D;D;D;D;D;D;D;D;.
Sift4G	Uncertain	0.036	D;D;D;T;D;D;D;D;D;D;D;D;D
Polyphen		0.99	D;D;.;.;.;.;.;.;.;D;.;.;.
Vest4		0.22
MutPred		0.22		Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);Loss of phosphorylation at S37 (P = 0.0354);
MVP		0.38
MPC		0.49
ClinPred		0.56	D
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-304521;