NM_182623.3:c.543A>G

Variant names:

• chr1-16059513-T-C
• rs2863452
• NM_182623.3:c.543A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182623.3(FAM131C):​c.543A>G​(p.Gln181Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,590,146 control chromosomes in the GnomAD database, including 446,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37338 hom., cov: 29)
  • Exomes 𝑓: 0.75 (409197 hom.)
• Consequence: FAM131C NM_182623.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.530
• Publications: 11 publications found

Genes affected

FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-16059513-T-C is Benign according to our data. Variant chr1-16059513-T-C is described in ClinVar as Benign. ClinVar VariationId is 1240760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182623.3. 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
	FAM131C	NM_182623.3	MANE Select	c.543A>G	p.Gln181Gln	synonymous	Exon 6 of 7	NP_872429.2	Q96AQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	ENST00000375662.5	TSL:1 MANE Select	c.543A>G	p.Gln181Gln	synonymous	Exon 6 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.507A>G	p.Gln169Gln	synonymous	Exon 5 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.360A>G	p.Gln120Gln	synonymous	Exon 5 of 6	ENSP00000574434.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 105879 AN: 150510 Hom.: 37327 Cov.: 29

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.757

GnomAD2 exomes AF: 0.765 AC: 180757 AN: 236330 AF XY: 0.768

Gnomad AFR exome AF: 0.524

Gnomad AMR exome AF: 0.869

Gnomad ASJ exome AF: 0.770

Gnomad EAS exome AF: 0.825

Gnomad FIN exome AF: 0.671

Gnomad NFE exome AF: 0.758

Gnomad OTH exome AF: 0.774

GnomAD4 exome AF: 0.753 AC: 1084590 AN: 1439518 Hom.: 409197 Cov.: 63 AF XY: 0.756 AC XY: 540372 AN XY: 714428

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.521 AC: 16893 AN: 32450

American (AMR) AF: 0.856 AC: 37028 AN: 43236

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 19418 AN: 25462

East Asian (EAS) AF: 0.840 AC: 32841 AN: 39078

South Asian (SAS) AF: 0.812 AC: 68769 AN: 84658

European-Finnish (FIN) AF: 0.678 AC: 35052 AN: 51734

Middle Eastern (MID) AF: 0.798 AC: 4528 AN: 5674

European-Non Finnish (NFE) AF: 0.752 AC: 825562 AN: 1097886

Other (OTH) AF: 0.750 AC: 44499 AN: 59340

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.703 AC: 105933 AN: 150628 Hom.: 37338 Cov.: 29 AF XY: 0.705 AC XY: 51836 AN XY: 73526

African (AFR) AF: 0.544 AC: 22236 AN: 40902

American (AMR) AF: 0.811 AC: 12333 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2589 AN: 3436

East Asian (EAS) AF: 0.827 AC: 4229 AN: 5116

South Asian (SAS) AF: 0.817 AC: 3836 AN: 4696

European-Finnish (FIN) AF: 0.683 AC: 7135 AN: 10442

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.756 AC: 51081 AN: 67542

Other (OTH) AF: 0.756 AC: 1584 AN: 2094

Alfa AF: 0.739 Hom.: 14545

Asia WGS AF: 0.767 AC: 2664 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs2863452; hg19: chr1-16386008; COSMIC: COSV65153327; COSMIC: COSV65153327;