Genetic Variant FAM9C:p.Asp73Tyr (chrX-13040870-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars). 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

0 publications found

Variant links:

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]

FAM9C links:

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ACMG classification

Classification was made for transcript

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_174901.6. 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
	FAM9C	NM_174901.6	MANE Select	c.217G>T	p.Asp73Tyr	missense splice_region	Exon 5 of 8	NP_777561.1	Q8IZT9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM9C	ENST00000380625.8	TSL:1 MANE Select	c.217G>T	p.Asp73Tyr	missense splice_region	Exon 5 of 8	ENSP00000369999.3	Q8IZT9
FAM9C	ENST00000333995.7	TSL:1	c.217G>T	p.Asp73Tyr	missense splice_region	Exon 5 of 7	ENSP00000334430.3	Q8IZT9
FAM9C	ENST00000542843.5	TSL:1	c.*1875G>T		3_prime_UTR	Exon 4 of 6	ENSP00000439185.1	G3V1I3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

140889

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1013948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

297148

African (AFR)

AF:

0.00

AC:

AN:

23866

American (AMR)

AF:

0.00

AC:

AN:

26913

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17942

East Asian (EAS)

AF:

0.00

AC:

AN:

28701

South Asian (SAS)

AF:

0.00

AC:

AN:

43454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3048

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

787850

Other (OTH)

AF:

0.00

AC:

AN:

42872

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.25

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.55

M_CAP

Benign

0.0052

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.9

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-6.7

REVEL

Benign

0.12

Sift

Uncertain

0.0040

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.61

MutPred

0.42

Loss of disorder (P = 0.0055)

MVP

0.24

MPC

0.083

ClinPred

0.51

GERP RS

0.59

Varity_R

0.25

gMVP

0.47

Mutation Taster

=74/26

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over