NM_006771.4:c.1306A>G

Variant names:

• chr17-41437477-T-C
• rs1209156969
• NM_006771.4:c.1306A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006771.4(KRT38):​c.1306A>G​(p.Ser436Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,404,334 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: KRT38 NM_006771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.171

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2024771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT38	NM_006771.4	c.1306A>G	p.Ser436Gly	missense_variant	Exon 7 of 7	ENST00000246646.4	NP_006762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT38	ENST00000246646.4	c.1306A>G	p.Ser436Gly	missense_variant	Exon 7 of 7	1	NM_006771.4	ENSP00000246646.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000285 AC: 4 AN: 1404334 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2 AN XY: 698138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000943

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1306A>G (p.S436G) alteration is located in exon 7 (coding exon 7) of the KRT38 gene. This alteration results from a A to G substitution at nucleotide position 1306, causing the serine (S) at amino acid position 436 to be replaced by a glycine (G). 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	0.078
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	9.3
DANN	Benign	0.92
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.23
Sift	Benign	0.10	T
Sift4G	Benign	0.21	T
Polyphen		0.88	P
Vest4		0.16
MutPred		0.22		Loss of glycosylation at S436 (P = 0.001);
MVP		0.77
MPC		0.038
ClinPred		0.27	T
GERP RS		2.3
Varity_R		0.10
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1209156969; hg19: chr17-39593729;