rs529308915

Variant names:

• chr17-41437419-C-A
• NM_006771.4:c.1364G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41437419-C-A
• chr17-41437419-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006771.4(KRT38):​c.1364G>T​(p.Arg455Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,411,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R455Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KRT38 NM_006771.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

Genes affected

KRT38 (HGNC:6456): (keratin 38) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08777553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT38	NM_006771.4	c.1364G>T	p.Arg455Leu	missense_variant	Exon 7 of 7	ENST00000246646.4	NP_006762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT38	ENST00000246646.4	c.1364G>T	p.Arg455Leu	missense_variant	Exon 7 of 7	1	NM_006771.4	ENSP00000246646.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411920 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701134

Gnomad4 AFR exome AF: 0.0000338

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.087	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	0.063	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.39	B
Vest4		0.27
MutPred		0.27		Loss of methylation at R455 (P = 0.0233);
MVP		0.38
MPC		0.046
ClinPred		0.20	T
GERP RS		-0.99
Varity_R		0.074
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39593671; COSMIC: COSV55847380;