16-260006-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_032039.4(FAM234A):c.423G>A(p.Ser141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,613,406 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (211 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (206 hom.)
• Consequence: FAM234A NM_032039.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.22

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-260006-G-A is Benign according to our data. Variant chr16-260006-G-A is described in ClinVar as [Benign]. Clinvar id is 785515.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.096 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM234A	NM_032039.4	c.423G>A	p.Ser141=	synonymous_variant	5/13	ENST00000399932.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM234A	ENST00000399932.8	c.423G>A	p.Ser141=	synonymous_variant	5/13	1	NM_032039.4	P1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4276 AN: 152182 Hom.: 210 Cov.: 33

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00896

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00690 AC: 1716 AN: 248830 Hom.: 86 AF XY: 0.00544 AC XY: 735 AN XY: 135106

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.000995

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00293 AC: 4276 AN: 1461106 Hom.: 206 Cov.: 32 AF XY: 0.00254 AC XY: 1848 AN XY: 726932

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.00327

Gnomad4 ASJ exome AF: 0.000765

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.0000566

Gnomad4 NFE exome AF: 0.0000980

Gnomad4 OTH exome AF: 0.00558

GnomAD4 genome AF: 0.0281 AC: 4287 AN: 152300 Hom.: 211 Cov.: 33 AF XY: 0.0276 AC XY: 2058 AN XY: 74482

Gnomad4 AFR AF: 0.0985

Gnomad4 AMR AF: 0.00895

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0133 Hom.: 62

Bravo AF: 0.0320

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.071
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13335497; hg19: chr16-310005; COSMIC: COSV56994706; COSMIC: COSV56994706;