X-8791373-T-C

Variant names:

• chrX-8791373-T-C
• rs151083543
• NM_174951.3:c.937A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_174951.3(FAM9A):​c.937A>G​(p.Lys313Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,200,057 control chromosomes in the GnomAD database, including 2 homozygotes. There are 415 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K313R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., 18 hem., cov: 24)
  • Exomes 𝑓: 0.0012 (2 hom. 397 hem.)
• Consequence: FAM9A NM_174951.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.295
• Publications: 1 publications found

Genes affected

FAM9A (HGNC:18403): (family with sequence similarity 9 member A) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be a nuclear protein that is localized to the nucleolus, and has some similarity to a synaptonemal complex protein. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00835219).
• BS2: High Hemizygotes in GnomAd4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174951.3. 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
	FAM9A	NM_174951.3	MANE Select	c.937A>G	p.Lys313Glu	missense	Exon 9 of 10	NP_777611.1	Q8IZU1
	FAM9A	NM_001171186.1		c.937A>G	p.Lys313Glu	missense	Exon 9 of 10	NP_001164657.1	Q8IZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM9A	ENST00000381003.7	TSL:1 MANE Select	c.937A>G	p.Lys313Glu	missense	Exon 9 of 10	ENSP00000370391.3	Q8IZU1
	FAM9A	ENST00000543214.1	TSL:1	c.937A>G	p.Lys313Glu	missense	Exon 9 of 10	ENSP00000440163.1	Q8IZU1

Frequencies

GnomAD3 genomes AF: 0.000632 AC: 71 AN: 112408 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000378

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000787 AC: 137 AN: 174013 AF XY: 0.000908

Gnomad AFR exome AF: 0.000234

Gnomad AMR exome AF: 0.0000792

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000380

Gnomad NFE exome AF: 0.00154

Gnomad OTH exome AF: 0.000468

GnomAD4 exome AF: 0.00117 AC: 1276 AN: 1087649 Hom.: 2 Cov.: 27 AF XY: 0.00112 AC XY: 397 AN XY: 354167

African (AFR) AF: 0.000153 AC: 4 AN: 26060

American (AMR) AF: 0.000177 AC: 6 AN: 33876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19068

East Asian (EAS) AF: 0.00 AC: 0 AN: 30022

South Asian (SAS) AF: 0.000135 AC: 7 AN: 51927

European-Finnish (FIN) AF: 0.000297 AC: 12 AN: 40351

Middle Eastern (MID) AF: 0.000740 AC: 3 AN: 4056

European-Non Finnish (NFE) AF: 0.00141 AC: 1180 AN: 836610

Other (OTH) AF: 0.00140 AC: 64 AN: 45679

GnomAD4 genome AF: 0.000632 AC: 71 AN: 112408 Hom.: 0 Cov.: 24 AF XY: 0.000521 AC XY: 18 AN XY: 34560

African (AFR) AF: 0.0000324 AC: 1 AN: 30906

American (AMR) AF: 0.000378 AC: 4 AN: 10578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3608

South Asian (SAS) AF: 0.00 AC: 0 AN: 2742

European-Finnish (FIN) AF: 0.000163 AC: 1 AN: 6140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00122 AC: 65 AN: 53340

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.000839 Hom.: 36

Bravo AF: 0.000661

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00134 AC: 9

ExAC AF: 0.000931 AC: 113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.86
DEOGEN2	Benign	0.0020	T
FATHMM_MKL	Benign	0.00056	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.00080	T
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.35	N
PhyloP100		0.29
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.0070
Sift	Benign	0.52	T
Sift4G	Benign	0.27	T
Polyphen		0.0040	B
Vest4		0.063
MVP		0.12
MPC		0.071
ClinPred		0.0020	T
GERP RS		-0.72
Varity_R		0.12
gMVP		0.0059
Mutation Taster		=100/0	polymorphism (auto)

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: rs151083543; hg19: chrX-8759414;