X-34943450-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P207L) has been classified 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11543131).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152631.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47B	NM_152631.3	MANE Select	c.619C>A	p.Pro207Thr	missense	Exon 1 of 1	NP_689844.2	Q8NA70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47B	ENST00000329357.6	TSL:6 MANE Select	c.619C>A	p.Pro207Thr	missense	Exon 1 of 1	ENSP00000328307.5	Q8NA70

Frequencies

GnomAD3 genomes AF: 0.0000182 AC: 2 AN: 109885 Hom.: 0 Cov.: 22

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

African (AFR) AF: 0.00 AC: 0 AN: 30197

American (AMR) AF: 0.00 AC: 0 AN: 10410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2622

East Asian (EAS) AF: 0.000584 AC: 2 AN: 3424

South Asian (SAS) AF: 0.00 AC: 0 AN: 2452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52497

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-2.5
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1602051712; hg19: chrX-34961567;