16-254423-C-T

Variant names:

• chr16-254423-C-T
• NM_032039.4:c.10C>T

Variant summary

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

The NM_032039.4(FAM234A):​c.10C>T​(p.His4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM234A NM_032039.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0980

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 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=0.06692746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM234A	NM_032039.4	c.10C>T	p.His4Tyr	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.10C>T	p.His4Tyr	missense_variant	Exon 3 of 13	1	NM_032039.4	ENSP00000382814.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461690 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727168

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.10C>T (p.H4Y) alteration is located in exon 3 (coding exon 1) of the FAM234A gene. This alteration results from a C to T substitution at nucleotide position 10, causing the histidine (H) at amino acid position 4 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	2.1
DANN	Benign	0.95
DEOGEN2	Benign	0.015	T;.;.;.;.;.;.;.;.;T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.69	.;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.067	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N;N;N;D;N;N;N;N;N;N;N;N;.
REVEL	Benign	0.13
Sift	Uncertain	0.022	D;D;D;T;D;D;D;D;D;D;D;D;.
Sift4G	Uncertain	0.048	D;T;T;T;T;T;T;T;T;D;T;T;D
Polyphen		0.23	B;B;.;.;.;.;.;.;.;B;.;.;.
Vest4		0.14
MutPred		0.10		Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);Gain of phosphorylation at H4 (P = 0.0097);
MVP		0.11
MPC		0.21
ClinPred		0.13	T
GERP RS		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.044
gMVP		0.26

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: chr16-304422;