17-41140282-C-T

Variant names:

• chr17-41140282-C-T
• rs774069745
• NM_030976.2:c.206G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030976.2(KRTAP4-6):​c.206G>A​(p.Cys69Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,444,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: KRTAP4-6 NM_030976.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.713
• Publications: 0 publications found

Genes affected

KRTAP4-6 (HGNC:18909): (keratin associated protein 4-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29625696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030976.2. 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
	KRTAP4-6	NM_030976.2	MANE Select	c.206G>A	p.Cys69Tyr	missense	Exon 1 of 1	NP_112238.1	Q9BYQ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-6	ENST00000345847.5	TSL:6 MANE Select	c.206G>A	p.Cys69Tyr	missense	Exon 1 of 1	ENSP00000328270.5	Q9BYQ5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246214 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: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1444438 Hom.: 0 Cov.: 37 AF XY: 0.00000139 AC XY: 1 AN XY: 719704

African (AFR) AF: 0.00 AC: 0 AN: 23710

American (AMR) AF: 0.00 AC: 0 AN: 43236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 85856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108642

Other (OTH) AF: 0.0000340 AC: 2 AN: 58746

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000167 AC: 2

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	Benign	0.29
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.064	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		0.71
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.086
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Vest4		0.22
MutPred		0.64		Loss of glycosylation at S68 (P = 0.1132)
MVP		0.25
MPC		0.087
ClinPred		0.67	D
GERP RS		2.3
PromoterAI		0.0044	Neutral
Varity_R		0.46
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs774069745; hg19: chr17-39296534;