NM_006771.4:c.827T>C

Variant names:

• chr17-41438764-A-G
• rs1247780609
• NM_006771.4:c.827T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006771.4(KRT38):​c.827T>C​(p.Met276Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: KRT38 NM_006771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

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.827T>C	p.Met276Thr	missense	Exon 4 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.827T>C	p.Met276Thr	missense	Exon 4 of 7	ENSP00000246646.3	O76015
	ENSG00000234859	ENST00000731569.1		n.134-5160A>G		intron	N/A
	ENSG00000234859	ENST00000731574.1		n.718-9070A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151914 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 59

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151914 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74200

African (AFR) AF: 0.00 AC: 0 AN: 41342

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Uncertain	0.74	D
Eigen	Benign	-0.068
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.60
Sift	Benign	0.18	T
Sift4G	Benign	0.10	T
Polyphen		0.028	B
Vest4		0.80
MutPred		0.76		Loss of catalytic residue at V272 (P = 0.0171)
MVP		0.80
MPC		0.058
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.25
gMVP		0.19

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: rs1247780609; hg19: chr17-39595016;