7-117129846-C-A

Variant names:

• chr7-117129846-C-A
• rs1790596216
• NM_001369598.1:c.448C>A
• ST7 p.Arg150Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001369598.1(ST7):​c.448C>A​(p.Arg150Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R150R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ST7 NM_001369598.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.006494
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.934
• Publications: 0 publications found

Genes affected

ST7 (HGNC:11351): (suppression of tumorigenicity 7) The gene for this product maps to a region on chromosome 7 identified as an autism-susceptibility locus. Mutation screening of the entire coding region in autistic individuals failed to identify phenotype-specific variants, suggesting that coding mutations for this gene are unlikely to be involved in the etiology of autism. The function of this gene product has not been determined. Transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

ST7-AS2 (HGNC:16044): (ST7 antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP7: Synonymous conserved (PhyloP=0.934 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369598.1. 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
	ST7	NM_001369598.1	MANE Select	c.448C>A	p.Arg150Arg	splice_region synonymous	Exon 4 of 16	NP_001356527.1	H7BXS2
	ST7	NM_021908.3		c.448C>A	p.Arg150Arg	splice_region synonymous	Exon 4 of 16	NP_068708.1	X5DRA0
	ST7	NM_001369601.1		c.448C>A	p.Arg150Arg	splice_region synonymous	Exon 4 of 16	NP_001356530.1	E7EPD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST7	ENST00000323984.8	TSL:5 MANE Select	c.448C>A	p.Arg150Arg	splice_region synonymous	Exon 4 of 16	ENSP00000325673.3	H7BXS2
	ST7	ENST00000265437.9	TSL:1	c.448C>A	p.Arg150Arg	splice_region synonymous	Exon 4 of 16	ENSP00000265437.5	Q9NRC1-1
	ST7	ENST00000393451.7	TSL:1	c.448C>A	p.Arg150Arg	splice_region synonymous	Exon 4 of 15	ENSP00000377097.3	Q9NRC1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456614 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724624

⚠️ 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: 33122

American (AMR) AF: 0.00 AC: 0 AN: 43750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109480

Other (OTH) AF: 0.00 AC: 0 AN: 60134

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0065
dbscSNV1_RF	Benign	0.16
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1790596216; hg19: chr7-116769900; COSMIC: COSV106395480; COSMIC: COSV106395480;