rs368965856

Variant names:

• chrX-13040870-C-A
• rs368965856
• NM_174901.6:c.217G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-13040870-C-A
• chrX-13040870-C-T

Variant summary

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

The NM_174901.6(FAM9C):​c.217G>T​(p.Asp73Tyr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. D73N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: FAM9C NM_174901.6 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

Genes affected

FAM9C (HGNC:18405): (family with sequence similarity 9 member C) 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM9C	NM_174901.6	c.217G>T	p.Asp73Tyr	missense_variant, splice_region_variant	Exon 5 of 8	ENST00000380625.8	NP_777561.1
FAM9C	XM_024452348.2	c.529G>T	p.Asp177Tyr	missense_variant, splice_region_variant	Exon 5 of 7		XP_024308116.2
FAM9C	XM_005274460.4	c.217G>T	p.Asp73Tyr	missense_variant, splice_region_variant	Exon 5 of 8		XP_005274517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM9C	ENST00000380625.8	c.217G>T	p.Asp73Tyr	missense_variant, splice_region_variant	Exon 5 of 8	1	NM_174901.6	ENSP00000369999.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1013948 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 297148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.25	T;T
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.0052	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.7	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.12	T;T
Polyphen		1.0	D;D
Vest4		0.61
MutPred		0.42		Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);
MVP		0.24
MPC		0.083
ClinPred		0.51	D
GERP RS		0.59
Varity_R		0.25
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs368965856; hg19: chrX-13058989;