NM_174901.6:c.183-10T>C

Variant names:

• chrX-13042959-A-G
• rs1057522761
• NM_174901.6:c.183-10T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_174901.6(FAM9C):​c.183-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,182,082 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: FAM9C NM_174901.6 intron
• Scores: Splicing: ADA: 0.00001723
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-13042959-A-G is Benign according to our data. Variant chrX-13042959-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 387318.Status of the report is criteria_provided_single_submitter, 1 stars.

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.183-10T>C		intron	N/A	NP_777561.1	Q8IZT9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM9C	ENST00000380625.8	TSL:1 MANE Select	c.183-10T>C		intron	N/A	ENSP00000369999.3	Q8IZT9
	FAM9C	ENST00000333995.7	TSL:1	c.183-10T>C		intron	N/A	ENSP00000334430.3	Q8IZT9
	FAM9C	ENST00000542843.5	TSL:1	c.183-10T>C		intron	N/A	ENSP00000439185.1	G3V1I3

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112424 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000648

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000647 AC: 1 AN: 154493 AF XY: 0.00

Gnomad AFR exome AF: 0.0000788

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 AF: 9.35e-7 AC: 1 AN: 1069658 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 346274

African (AFR) AF: 0.0000400 AC: 1 AN: 24998

American (AMR) AF: 0.00 AC: 0 AN: 28890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17711

East Asian (EAS) AF: 0.00 AC: 0 AN: 29969

South Asian (SAS) AF: 0.00 AC: 0 AN: 49061

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 830471

Other (OTH) AF: 0.00 AC: 0 AN: 44834

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112424 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34564

African (AFR) AF: 0.0000648 AC: 2 AN: 30872

American (AMR) AF: 0.00 AC: 0 AN: 10670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3622

South Asian (SAS) AF: 0.00 AC: 0 AN: 2728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6131

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53311

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.33
PhyloP100		-0.21
PromoterAI		0.051	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs1057522761; hg19: chrX-13061078;