16-254565-C-G

Variant names:

• chr16-254565-C-G
• rs765566976
• NM_032039.4:c.152C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032039.4(FAM234A):​c.152C>G​(p.Ala51Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A51E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM234A NM_032039.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27111065).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032039.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM234A	NM_032039.4	MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 3 of 13	NP_114428.1	Q9H0X4-1
	FAM234A	NM_001284497.2		c.152C>G	p.Ala51Gly	missense	Exon 3 of 13	NP_001271426.1	Q9H0X4-1
	FAM234A	NR_104317.2		n.328C>G		non_coding_transcript_exon	Exon 3 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM234A	ENST00000399932.8	TSL:1 MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 3 of 13	ENSP00000382814.3	Q9H0X4-1
	FAM234A	ENST00000301678.7	TSL:1	c.152C>G	p.Ala51Gly	missense	Exon 3 of 13	ENSP00000301678.3	Q9H0X4-1
	FAM234A	ENST00000970193.1		c.152C>G	p.Ala51Gly	missense	Exon 3 of 14	ENSP00000640252.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.021
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.79	T
PhyloP100		1.5
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.074
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.30		Loss of stability (P = 0.0765)
MVP		0.43
MPC		0.56
ClinPred		0.98	D
GERP RS		2.9
PromoterAI		-0.043	Neutral
Varity_R		0.11
gMVP		0.59

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

Other links and lift over

dbSNP: rs765566976; hg19: chr16-304564;