17-41438150-G-A

Variant names:

• chr17-41438150-G-A
• rs2018750789
• NM_006771.4:c.1184C>T

Variant summary

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

The NM_006771.4(KRT38):​c.1184C>T​(p.Thr395Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,894 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: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: KRT38 NM_006771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

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]

ENSG00000234859 (HGNC:):

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=0.33310074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006771.4. 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
	KRT38	NM_006771.4	MANE Select	c.1184C>T	p.Thr395Ile	missense	Exon 6 of 7	NP_006762.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT38	ENST00000246646.4	TSL:1 MANE Select	c.1184C>T	p.Thr395Ile	missense	Exon 6 of 7	ENSP00000246646.3	O76015
	ENSG00000234859	ENST00000731569.1		n.134-5774G>A		intron	N/A
	ENSG00000234859	ENST00000731574.1		n.718-9684G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.26
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.034	D
Polyphen		0.0020	B
Vest4		0.41
MutPred		0.48		Loss of disorder (P = 0.0531)
MVP		0.77
MPC		0.042
ClinPred		0.90	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.15
Mutation Taster		=94/6	polymorphism

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: rs2018750789; hg19: chr17-39594402;