chrX-52650363-A-T

Variant names:

• chrX-52650363-A-T
• rs377004276
• NM_173358.2:c.320T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173358.2(SSX7):​c.320T>A​(p.Ile107Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,791 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. 13/20 in silico tools predict a benign outcome for this variant. 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. I107T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SSX7 NM_173358.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 0 publications found

Genes affected

SSX7 (HGNC:19653): (SSX family member 7) The product of this gene belongs to the family of highly homologous synovial sarcoma X (SSX) breakpoint proteins. These proteins may function as transcriptional repressors. They are also capable of eliciting spontaneously humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. SSX1, SSX2 and SSX4 genes have been involved in the t(X;18) translocation characteristically found in all synovial sarcomas. This gene appears not to be involved in this type of chromosome translocation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09043467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173358.2. 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
	SSX7	NM_173358.2	MANE Select	c.320T>A	p.Ile107Asn	missense	Exon 5 of 8	NP_775494.1	Q7RTT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX7	ENST00000298181.6	TSL:5 MANE Select	c.320T>A	p.Ile107Asn	missense	Exon 5 of 8	ENSP00000298181.5	Q7RTT5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096791 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362355

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26366

American (AMR) AF: 0.00 AC: 0 AN: 35177

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30177

South Asian (SAS) AF: 0.00 AC: 0 AN: 54078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40477

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4080

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841049

Other (OTH) AF: 0.00 AC: 0 AN: 46030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.64
DEOGEN2	Benign	0.0086	T
FATHMM_MKL	Benign	0.00034	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.00070	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.27
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.046
Sift	Benign	0.26	T
Sift4G	Uncertain	0.053	T
Polyphen		0.0030	B
Vest4		0.19
MutPred		0.29		Loss of stability (P = 0.0164)
MVP		0.23
MPC		0.022
ClinPred		0.33	T
GERP RS		-1.1
Varity_R		0.16
gMVP		0.021
Mutation Taster		=100/0	polymorphism

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: rs377004276; hg19: chrX-52679413;