chrX-34130607-G-A

Variant names:

• chrX-34130607-G-A
• rs1922423638
• NM_203408.4:c.1672C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203408.4(FAM47A):​c.1672C>T​(p.Pro558Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: FAM47A NM_203408.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160

Genes affected

FAM47A (HGNC:29962): (family with sequence similarity 47 member A)

ENSG00000233928 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08099869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47A	NM_203408.4	c.1672C>T	p.Pro558Ser	missense_variant	Exon 1 of 1	ENST00000346193.5	NP_981953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47A	ENST00000346193.5	c.1672C>T	p.Pro558Ser	missense_variant	Exon 1 of 1	6	NM_203408.4	ENSP00000345029.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 110281 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32673 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 110329 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32733

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1672C>T (p.P558S) alteration is located in exon 1 (coding exon 1) of the FAM47A gene. This alteration results from a C to T substitution at nucleotide position 1672, causing the proline (P) at amino acid position 558 to be replaced by a serine (S). 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	Benign	0.17
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.62
DANN	Benign	0.25
DEOGEN2	Benign	0.023	T;.
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.00087	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Benign	0.039
Sift	Benign	0.51	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.51	P;.
Vest4		0.042
MutPred		0.15		Gain of phosphorylation at P558 (P = 0.0075);.;
MVP		0.043
MPC		0.20
ClinPred		0.24	T
GERP RS		-1.4
Varity_R		0.055
gMVP		0.13

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: rs1922423638; hg19: chrX-34148724;