17-41420919-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003770.5(KRT37):​c.1309G>C​(p.Gly437Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,613,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

KRT37
NM_003770.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.353
Variant links:
Genes affected
KRT37 (HGNC:6455): (keratin 37) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0051659048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT37NM_003770.5 linkc.1309G>C p.Gly437Arg missense_variant Exon 7 of 7 ENST00000225550.4 NP_003761.3 O76014

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT37ENST00000225550.4 linkc.1309G>C p.Gly437Arg missense_variant Exon 7 of 7 1 NM_003770.5 ENSP00000225550.3 O76014
ENSG00000234859ENST00000432258.1 linkn.2195-2435C>G intron_variant Intron 3 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.000250
AC:
38
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000830
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000382
AC:
96
AN:
251218
Hom.:
1
AF XY:
0.000442
AC XY:
60
AN XY:
135778
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00496
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000425
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000167
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000211
AC:
308
AN:
1461704
Hom.:
1
Cov.:
30
AF XY:
0.000254
AC XY:
185
AN XY:
727158
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.00406
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000429
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000908
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000250
AC:
38
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.000322
AC XY:
24
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000831
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000812
Hom.:
0
Bravo
AF:
0.000268
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000288
AC:
35
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1309G>C (p.G437R) alteration is located in exon 7 (coding exon 7) of the KRT37 gene. This alteration results from a G to C substitution at nucleotide position 1309, causing the glycine (G) at amino acid position 437 to be replaced by an arginine (R). 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
0.15
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
0.60
DANN
Benign
0.59
DEOGEN2
Benign
0.015
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.016
N
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.0052
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
-0.34
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.33
N
REVEL
Benign
0.18
Sift
Benign
0.26
T
Sift4G
Benign
0.57
T
Polyphen
0.37
B
Vest4
0.26
MVP
0.42
MPC
0.068
ClinPred
0.033
T
GERP RS
3.3
Varity_R
0.027
gMVP
0.059

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150463302; hg19: chr17-39577171; API