chr17-75817465-C-T

Variant names:

• chr17-75817465-C-T
• rs889448171
• NM_001080419.3:c.1244C>T

Variant summary

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

The NM_001080419.3(UNK):​c.1244C>T​(p.Ala415Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UNK NM_001080419.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1244C>T	p.Ala415Val	missense	Exon 9 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.1244C>T	p.Ala415Val	missense	Exon 9 of 16	ENSP00000464893.1	Q9C0B0
	UNK	ENST00000925670.1		c.1361C>T	p.Ala454Val	missense	Exon 10 of 17	ENSP00000595729.1
	UNK	ENST00000925669.1		c.1244C>T	p.Ala415Val	missense	Exon 9 of 16	ENSP00000595728.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 247936 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460812 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726586

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111510

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 32

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	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	0.90	L
PhyloP100		7.5
PrimateAI	Uncertain	0.72	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.69
MutPred		0.21		Gain of methylation at K414 (P = 0.0367)
MVP		0.093
MPC		1.2
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.43
gMVP		0.74

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: rs889448171; hg19: chr17-73813546;