X-34130553-G-A

Variant names:

• chrX-34130553-G-A
• rs77378325
• NM_203408.4:c.1726C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_203408.4(FAM47A):​c.1726C>T​(p.Arg576*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,238 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: FAM47A NM_203408.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 0 publications found

Genes affected

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

ENSG00000233928 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203408.4. 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
	FAM47A	NM_203408.4	MANE Select	c.1726C>T	p.Arg576*	stop_gained	Exon 1 of 1	NP_981953.2	Q5JRC9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47A	ENST00000346193.5	TSL:6 MANE Select	c.1726C>T	p.Arg576*	stop_gained	Exon 1 of 1	ENSP00000345029.3	Q5JRC9
	ENSG00000233928	ENST00000653446.1		n.390+53984G>A		intron	N/A
	ENSG00000233928	ENST00000656777.1		n.452+53984G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098238 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363592

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842137

Other (OTH) AF: 0.0000217 AC: 1 AN: 46097

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Benign	0.94
FATHMM_MKL	Benign	0.00089	N
PhyloP100		-0.65
Vest4		0.020
GERP RS		-1.0
Mutation Taster		=190/10	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: rs77378325; hg19: chrX-34148670;