X-34130361-C-G

Variant names:

• chrX-34130361-C-G
• rs766609741
• NM_203408.4:c.1918G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203408.4(FAM47A):​c.1918G>C​(p.Glu640Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,221 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E640K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: FAM47A NM_203408.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• Publications: 0 publications found

Genes affected

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

ENSG00000233928 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044118106).

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.1918G>C	p.Glu640Gln	missense	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.1918G>C	p.Glu640Gln	missense	Exon 1 of 1	ENSP00000345029.3	Q5JRC9
	ENSG00000233928	ENST00000653446.1		n.390+53792C>G		intron	N/A
	ENSG00000233928	ENST00000656777.1		n.452+53792C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098221 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363579

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40529

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

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842130

Other (OTH) AF: 0.00 AC: 0 AN: 46096

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0070
DANN	Benign	0.10
DEOGEN2	Benign	0.0047	T
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.27	N
PhyloP100		-2.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.0090
Sift	Benign	0.81	T
Sift4G	Benign	0.64	T
Polyphen		0.021	B
Vest4		0.046
MutPred		0.17		Gain of MoRF binding (P = 0.0343)
MVP		0.043
MPC		0.25
ClinPred		0.015	T
GERP RS		-0.87
Varity_R		0.054
gMVP		0.043
Mutation Taster		=100/0	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: rs766609741; hg19: chrX-34148478;