17-41438232-T-G

Variant names:

• chr17-41438232-T-G
• rs2018752317
• NM_006771.4:c.1102A>C

Variant summary

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

The NM_006771.4(KRT38):​c.1102A>C​(p.Asn368His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRT38 NM_006771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.691

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 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
KRT38	NM_006771.4	c.1102A>C	p.Asn368His	missense_variant	Exon 6 of 7	ENST00000246646.4	NP_006762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT38	ENST00000246646.4	c.1102A>C	p.Asn368His	missense_variant	Exon 6 of 7	1	NM_006771.4	ENSP00000246646.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1102A>C (p.N368H) alteration is located in exon 6 (coding exon 6) of the KRT38 gene. This alteration results from a A to C substitution at nucleotide position 1102, causing the asparagine (N) at amino acid position 368 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Benign	0.058
Eigen_PC	Benign	-0.054
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.46		Loss of stability (P = 0.0921);
MVP		0.82
MPC		0.28
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.29
gMVP		0.10

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: rs2018752317; hg19: chr17-39594484;