12-13055618-C-T

Variant names:

• chr12-13055618-C-T
• rs4763924
• NM_020853.2:c.105C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_020853.2(FAM234B):​c.105C>T​(p.Asp35Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,744 control chromosomes in the GnomAD database, including 32,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (5195 hom., cov: 32)
  • Exomes 𝑓: 0.17 (27236 hom.)
• Consequence: FAM234B NM_020853.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.123

Genes affected

FAM234B (HGNC:29288): (family with sequence similarity 234 member B) Predicted to be located in Golgi apparatus and cytoskeleton. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 12-13055618-C-T is Benign according to our data. Variant chr12-13055618-C-T is described in ClinVar as [Benign]. Clinvar id is 3060079.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.123 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM234B	NM_020853.2	c.105C>T	p.Asp35Asp	synonymous_variant	Exon 2 of 13	ENST00000197268.13	NP_065904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM234B	ENST00000197268.13	c.105C>T	p.Asp35Asp	synonymous_variant	Exon 2 of 13	1	NM_020853.2	ENSP00000197268.8
FAM234B	ENST00000416494.6	n.105C>T		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000394063.2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35953 AN: 151946 Hom.: 5170 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.245 AC: 61543 AN: 251330 Hom.: 9489 AF XY: 0.236 AC XY: 32067 AN XY: 135846

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.527

Gnomad SAS exome AF: 0.274

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.174 AC: 253903 AN: 1461680 Hom.: 27236 Cov.: 33 AF XY: 0.176 AC XY: 127622 AN XY: 727108

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.237 AC: 36034 AN: 152064 Hom.: 5195 Cov.: 32 AF XY: 0.243 AC XY: 18041 AN XY: 74322

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.226

Alfa AF: 0.176 Hom.: 3597

Bravo AF: 0.249

Asia WGS AF: 0.422 AC: 1467 AN: 3478

EpiCase AF: 0.146

EpiControl AF: 0.147

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FAM234B-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.5
DANN	Benign	0.33

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

LitVar

Other links and lift over

dbSNP: rs4763924; hg19: chr12-13208552; COSMIC: COSV52192519;