17-75815253-C-T

Variant names:

• chr17-75815253-C-T
• rs2143796334
• NM_001080419.3:c.961C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080419.3(UNK):​c.961C>T​(p.Gln321*) variant causes a stop gained, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UNK NM_001080419.3 stop_gained, splice_region
• Scores: Splicing: ADA: 0.9951
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.07
• Publications: 0 publications found

Genes affected

UNK (HGNC:29369): (unk zinc finger) Enables mRNA CDS binding activity. Involved in cell morphogenesis involved in neuron differentiation and negative regulation of cytoplasmic translation. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080419.3. 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
	UNK	NM_001080419.3	MANE Select	c.961C>T	p.Gln321*	stop_gained splice_region	Exon 7 of 16	NP_001073888.2	Q9C0B0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNK	ENST00000589666.6	TSL:1 MANE Select	c.961C>T	p.Gln321*	stop_gained splice_region	Exon 7 of 16	ENSP00000464893.1	Q9C0B0
	UNK	ENST00000925670.1		c.1078C>T	p.Gln360*	stop_gained splice_region	Exon 8 of 17	ENSP00000595729.1
	UNK	ENST00000925669.1		c.961C>T	p.Gln321*	stop_gained splice_region	Exon 7 of 16	ENSP00000595728.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.0021	T
PhyloP100		5.1
Vest4		0.86
GERP RS		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.83
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: rs2143796334; hg19: chr17-73811334; COSMIC: COSV53147232; COSMIC: COSV53147232;