rs10515808

Positions:

• chr5-160393924-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022090.5(FAM200C):​c.1567G>T​(p.Ala523Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,613,608 control chromosomes in the GnomAD database, including 7,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.075 (521 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6610 hom.)
• Consequence: FAM200C NM_022090.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

Genes affected

FAM200C (HGNC:30804): (family with sequence similarity 200 member C) Located in nucleoplasm. [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 (MetaRNN=0.00157395).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM200C	NM_022090.5	c.1567G>T	p.Ala523Ser	missense_variant	2/2	ENST00000408953.4	NP_071373.2
FAM200C	NM_001303251.2	c.1567G>T	p.Ala523Ser	missense_variant	3/3		NP_001290180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM200C	ENST00000408953.4	c.1567G>T	p.Ala523Ser	missense_variant	2/2	2	NM_022090.5	ENSP00000386184	P1
FAM200C	ENST00000523213.1	c.1567G>T	p.Ala523Ser	missense_variant	3/3	1		ENSP00000428831	P1

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11467 AN: 152114 Hom.: 521 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0864

GnomAD3 exomes AF: 0.0784 AC: 19511 AN: 248968 Hom.: 909 AF XY: 0.0815 AC XY: 10982 AN XY: 134766

Gnomad AFR exome AF: 0.0379

Gnomad AMR exome AF: 0.0485

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0766

Gnomad FIN exome AF: 0.0896

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.0871

GnomAD4 exome AF: 0.0915 AC: 133676 AN: 1461376 Hom.: 6610 Cov.: 32 AF XY: 0.0917 AC XY: 66632 AN XY: 727024

Gnomad4 AFR exome AF: 0.0364

Gnomad4 AMR exome AF: 0.0537

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.0762

Gnomad4 FIN exome AF: 0.0863

Gnomad4 NFE exome AF: 0.0988

Gnomad4 OTH exome AF: 0.0873

GnomAD4 genome AF: 0.0753 AC: 11469 AN: 152232 Hom.: 521 Cov.: 32 AF XY: 0.0743 AC XY: 5527 AN XY: 74422

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0663

Gnomad4 FIN AF: 0.0859

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0961 Hom.: 1582

Bravo AF: 0.0734

TwinsUK AF: 0.0990 AC: 367

ALSPAC AF: 0.0952 AC: 367

ESP6500AA AF: 0.0399 AC: 176

ESP6500EA AF: 0.102 AC: 881

ExAC AF: 0.0787 AC: 9552

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.4
DANN	Benign	0.68
DEOGEN2	Benign	0.0065	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.28	.;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.4	N;N
MutationTaster	Benign	1.0	P;P
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.0070
Sift	Benign	1.0	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0	B;B
Vest4		0.044
MPC		0.039
ClinPred		0.0015	T
GERP RS		1.0
Varity_R		0.030
gMVP		0.052

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: rs10515808; hg19: chr5-159820931; COSMIC: COSV68824928;