X-34943450-C-A

Variant names:

• chrX-34943450-C-A
• rs1602051712
• NM_152631.3:c.619C>A

Variant summary

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

The NM_152631.3(FAM47B):​c.619C>A​(p.Pro207Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 109,937 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
• Consequence: FAM47B NM_152631.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.50

Genes affected

FAM47B (HGNC:26659): (family with sequence similarity 47 member B)

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=0.11543131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47B	NM_152631.3	c.619C>A	p.Pro207Thr	missense_variant	Exon 1 of 1	ENST00000329357.6	NP_689844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47B	ENST00000329357.6	c.619C>A	p.Pro207Thr	missense_variant	Exon 1 of 1	6	NM_152631.3	ENSP00000328307.5

Frequencies

GnomAD3 genomes AF: 0.0000182 AC: 2 AN: 109885 Hom.: 0 Cov.: 22 AF XY: 0.0000310 AC XY: 1 AN XY: 32305

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000582

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 AF: 0.0000182 AC: 2 AN: 109937 Hom.: 0 Cov.: 22 AF XY: 0.0000309 AC XY: 1 AN XY: 32367

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.619C>A (p.P207T) alteration is located in exon 1 (coding exon 1) of the FAM47B gene. This alteration results from a C to A substitution at nucleotide position 619, causing the proline (P) at amino acid position 207 to be replaced by a threonine (T). 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	0.091
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.94
DEOGEN2	Benign	0.037	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.045
Sift	Benign	0.10	T
Sift4G	Benign	0.22	T
Polyphen		0.89	P
Vest4		0.041
MutPred		0.16		Gain of phosphorylation at P207 (P = 0.0187);
MVP		0.030
MPC		0.55
ClinPred		0.64	D
GERP RS		-0.47
Varity_R		0.12
gMVP		0.12

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: rs1602051712; hg19: chrX-34961567;