X-9025523-C-G

Position:

• chrX-9025523-C-G

Variant summary

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

The NM_205849.3(FAM9B):​c.553G>C​(p.Asp185His) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: FAM9B NM_205849.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0540

Genes affected

FAM9B (HGNC:18404): (family with sequence similarity 9 member B) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be localized to the nucleus as the protein contains several nuclear localization signals, and has similarity to a synaptonemal complex protein. [provided by RefSeq, Aug 2011]

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=0.15130123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM9B	NM_205849.3	c.553G>C	p.Asp185His	missense_variant	8/9	ENST00000327220.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9B	ENST00000327220.10	c.553G>C	p.Asp185His	missense_variant	8/9	1	NM_205849.3	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.553G>C (p.D185H) alteration is located in exon 7 (coding exon 7) of the FAM9B gene. This alteration results from a G to C substitution at nucleotide position 553, causing the aspartic acid (D) at amino acid position 185 to be replaced by a histidine (H). 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	0.33
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.028	.;T;T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.55	T;T;.
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	.;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.081
MutPred		0.16		.;Gain of catalytic residue at N186 (P = 0.0448);Gain of catalytic residue at N186 (P = 0.0448);
MVP		0.43
MPC		0.37
ClinPred		0.44	T
GERP RS		0.23
Varity_R		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-8993564;