17-75813129-C-T

Variant names:

• chr17-75813129-C-T
• rs779707258
• NM_001080419.3:c.674C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001080419.3(UNK):​c.674C>T​(p.Pro225Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000976 in 1,435,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: UNK NM_001080419.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.80
• Publications: 2 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 14 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.674C>T	p.Pro225Leu	missense	Exon 5 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.674C>T	p.Pro225Leu	missense	Exon 5 of 16	ENSP00000464893.1	Q9C0B0
	UNK	ENST00000925670.1		c.791C>T	p.Pro264Leu	missense	Exon 6 of 17	ENSP00000595729.1
	UNK	ENST00000925669.1		c.674C>T	p.Pro225Leu	missense	Exon 5 of 16	ENSP00000595728.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000148 AC: 3 AN: 203024 AF XY: 0.00000909

Gnomad AFR exome AF: 0.0000888

Gnomad AMR exome AF: 0.0000342

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000113

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000976 AC: 14 AN: 1435044 Hom.: 0 Cov.: 31 AF XY: 0.0000141 AC XY: 10 AN XY: 711458

African (AFR) AF: 0.0000609 AC: 2 AN: 32836

American (AMR) AF: 0.0000249 AC: 1 AN: 40164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.00 AC: 0 AN: 38354

South Asian (SAS) AF: 0.00 AC: 0 AN: 82394

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000819 AC: 9 AN: 1099156

Other (OTH) AF: 0.0000168 AC: 1 AN: 59456

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ExAC AF: 0.00000832 AC: 1

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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.89	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.26		Loss of catalytic residue at P224 (P = 0.0185)
MVP		0.28
MPC		2.6
ClinPred		0.92	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.48
gMVP		0.90
Mutation Taster		=37/63	disease causing

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: rs779707258; hg19: chr17-73809210; COSMIC: COSV99504936; COSMIC: COSV99504936;