rs2143796334

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-75815253-C-G
• chr17-75815253-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001080419.3(UNK):​c.961C>G​(p.Gln321Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000616 in 1,460,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: UNK NM_001080419.3 missense, splice_region
• Scores: Splicing: ADA: 0.1887
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12730375).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

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>G	p.Gln321Glu	missense 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>G	p.Gln321Glu	missense splice_region	Exon 7 of 16	ENSP00000464893.1	Q9C0B0
	UNK	ENST00000925670.1		c.1078C>G	p.Gln360Glu	missense splice_region	Exon 8 of 17	ENSP00000595729.1
	UNK	ENST00000925669.1		c.961C>G	p.Gln321Glu	missense splice_region	Exon 7 of 16	ENSP00000595728.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460312 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726436

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111198

Other (OTH) AF: 0.0000166 AC: 1 AN: 60312

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.0054	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.060
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.46	N
PhyloP100		5.1
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.38	T
Polyphen		0.011	B
Vest4		0.39
MutPred		0.13		Gain of catalytic residue at Q321 (P = 0.0403)
MVP		0.068
MPC		1.5
ClinPred		0.57	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.58
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.19
dbscSNV1_RF	Benign	0.31
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;