17-41619677-G-C

Variant names:

• chr17-41619677-G-C
• rs777503614
• NM_000422.3:c.1216C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000422.3(KRT17):​c.1216C>G​(p.Arg406Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRT17 NM_000422.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.36

Genes affected

KRT17 (HGNC:6427): (keratin 17) This gene encodes the type I intermediate filament chain keratin 17, expressed in nail bed, hair follicle, sebaceous glands, and other epidermal appendages. Mutations in this gene lead to Jackson-Lawler type pachyonychia congenita and steatocystoma multiplex. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT17	NM_000422.3	c.1216C>G	p.Arg406Gly	missense_variant	Exon 8 of 8	ENST00000311208.13	NP_000413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT17	ENST00000311208.13	c.1216C>G	p.Arg406Gly	missense_variant	Exon 8 of 8	1	NM_000422.3	ENSP00000308452.8
KRT17	ENST00000493253.5	n.1603C>G		non_coding_transcript_exon_variant	Exon 7 of 7	2
KRT17	ENST00000649249.1	n.492C>G		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249834 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135126

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459888 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726240

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;T
Eigen	Benign	0.030
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	.;T;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	.;N;.
REVEL	Uncertain	0.48
Sift	Benign	0.091	.;T;.
Sift4G	Benign	0.17	.;T;T
Polyphen		0.0010	B;B;.
Vest4		0.80, 0.81
MVP		0.86
MPC		0.41
ClinPred		0.77	D
GERP RS		4.4
Varity_R		0.15
gMVP		0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs777503614; hg19: chr17-39775929;