X-34943021-T-C

Variant names:

• chrX-34943021-T-C
• rs1602051324
• NM_152631.3:c.190T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152631.3(FAM47B):​c.190T>C​(p.Ser64Pro) 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: not found (cov: 23)
• Consequence: FAM47B NM_152631.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0350

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05914709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47B	NM_152631.3	c.190T>C	p.Ser64Pro	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.190T>C	p.Ser64Pro	missense_variant	Exon 1 of 1	6	NM_152631.3	ENSP00000328307.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.190T>C (p.S64P) alteration is located in exon 1 (coding exon 1) of the FAM47B gene. This alteration results from a T to C substitution at nucleotide position 190, causing the serine (S) at amino acid position 64 to be replaced by a proline (P). 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	0.16
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.27
DEOGEN2	Benign	0.0047	T
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.70	N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.013
Sift	Benign	0.50	T
Sift4G	Benign	0.45	T
Polyphen		0.024	B
Vest4		0.26
MVP		0.055
MPC		0.84
ClinPred		0.057	T
GERP RS		-0.44
Varity_R		0.48
gMVP		0.042

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: rs1602051324; hg19: chrX-34961138;