16-254559-C-A

Variant names:

• chr16-254559-C-A
• rs1252740487
• NM_032039.4:c.146C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032039.4(FAM234A):​c.146C>A​(p.Ala49Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A49G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM234A NM_032039.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26279306).

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.146C>A	p.Ala49Glu	missense	Exon 3 of 13	NP_114428.1	Q9H0X4-1
	FAM234A	NM_001284497.2		c.146C>A	p.Ala49Glu	missense	Exon 3 of 13	NP_001271426.1	Q9H0X4-1
	FAM234A	NR_104317.2		n.322C>A		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.146C>A	p.Ala49Glu	missense	Exon 3 of 13	ENSP00000382814.3	Q9H0X4-1
	FAM234A	ENST00000301678.7	TSL:1	c.146C>A	p.Ala49Glu	missense	Exon 3 of 13	ENSP00000301678.3	Q9H0X4-1
	FAM234A	ENST00000970193.1		c.146C>A	p.Ala49Glu	missense	Exon 3 of 14	ENSP00000640252.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727206

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.00078	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.52	P
Vest4		0.33
MutPred		0.38		Loss of methylation at R48 (P = 0.0521)
MVP		0.27
MPC		0.18
ClinPred		0.79	D
GERP RS		4.0
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.62
Mutation Taster		=90/10	polymorphism

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: rs1252740487; hg19: chr16-304558;