NM_006771.4:c.1279G>C

Variant names:

• chr17-41437504-C-G
• rs780324275
• NM_006771.4:c.1279G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006771.4(KRT38):​c.1279G>C​(p.Val427Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT38 NM_006771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.959
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06169969).

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.1279G>C	p.Val427Leu	missense	Exon 7 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.1279G>C	p.Val427Leu	missense	Exon 7 of 7	ENSP00000246646.3	O76015
	ENSG00000234859	ENST00000731569.1		n.134-6420C>G		intron	N/A
	ENSG00000234859	ENST00000731574.1		n.718-10330C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1409304 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700488

African (AFR) AF: 0.00 AC: 0 AN: 29332

American (AMR) AF: 0.00 AC: 0 AN: 33088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24144

East Asian (EAS) AF: 0.00 AC: 0 AN: 35228

South Asian (SAS) AF: 0.00 AC: 0 AN: 78928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4328

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093476

Other (OTH) AF: 0.00 AC: 0 AN: 58042

GnomAD4 genome Cov.: 33

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	0.10
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.0
DANN	Benign	0.74
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.96
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.21
Sift	Benign	0.67	T
Sift4G	Benign	0.32	T
Polyphen		0.049	B
Vest4		0.16
MutPred		0.18		Loss of glycosylation at T428 (P = 0.1065)
MVP		0.50
MPC		0.044
ClinPred		0.033	T
GERP RS		1.2
Varity_R		0.047
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs780324275; hg19: chr17-39593756;