16-254550-G-T

Variant names:

• chr16-254550-G-T
• rs192602168
• NM_032039.4:c.137G>T

Variant summary

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

The NM_032039.4(FAM234A):​c.137G>T​(p.Arg46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. R46W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: FAM234A NM_032039.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82
• Publications: 2 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=0.35798097).

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.137G>T	p.Arg46Leu	missense	Exon 3 of 13	NP_114428.1	Q9H0X4-1
	FAM234A	NM_001284497.2		c.137G>T	p.Arg46Leu	missense	Exon 3 of 13	NP_001271426.1	Q9H0X4-1
	FAM234A	NR_104317.2		n.313G>T		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.137G>T	p.Arg46Leu	missense	Exon 3 of 13	ENSP00000382814.3	Q9H0X4-1
	FAM234A	ENST00000301678.7	TSL:1	c.137G>T	p.Arg46Leu	missense	Exon 3 of 13	ENSP00000301678.3	Q9H0X4-1
	FAM234A	ENST00000970193.1		c.137G>T	p.Arg46Leu	missense	Exon 3 of 14	ENSP00000640252.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249542 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000454 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.66	T
PhyloP100		2.8
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.044	D
Polyphen		0.94	P
Vest4		0.61
MutPred		0.51		Loss of disorder (P = 0.0612)
MVP		0.41
MPC		0.59
ClinPred		0.78	D
GERP RS		2.6
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.39
Mutation Taster		=89/11	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: rs192602168; hg19: chr16-304549;