10-118336213-C-T

Position:

• chr10-118336213-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022063.3(FAM204A):​c.203G>A​(p.Cys68Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM204A NM_022063.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.84

Genes affected

FAM204A (HGNC:25794): (family with sequence similarity 204 member A)

FAM204A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM204A	NM_022063.3	c.203G>A	p.Cys68Tyr	missense_variant	3/9	ENST00000369183.9	NP_071346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM204A	ENST00000369183.9	c.203G>A	p.Cys68Tyr	missense_variant	3/9	1	NM_022063.3	ENSP00000358183.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461524 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.203G>A (p.C68Y) alteration is located in exon 3 (coding exon 1) of the FAM204A gene. This alteration results from a G to A substitution at nucleotide position 203, causing the cysteine (C) at amino acid position 68 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.3	D;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.78
MutPred		0.55		Gain of glycosylation at S70 (P = 0.1199);Gain of glycosylation at S70 (P = 0.1199);Gain of glycosylation at S70 (P = 0.1199);
MVP		0.33
MPC		0.93
ClinPred		0.95	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-120095725;