NM_001009931.3:c.6264C>A

Variant names:

• chr1-152215365-G-T
• rs144489730
• NM_001009931.3:c.6264C>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001009931.3(HRNR):​c.6264C>A​(p.Ser2088Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000089 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000023 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55
• Publications: 1 publications found

Genes affected

HRNR (HGNC:20846): (hornerin) Predicted to enable calcium ion binding activity and transition metal ion binding activity. Involved in cell envelope organization and establishment of skin barrier. Located in cornified envelope; keratohyalin granule; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 1-152215365-G-T is Benign according to our data. Variant chr1-152215365-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009931.3. 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
	HRNR	NM_001009931.3	MANE Select	c.6264C>A	p.Ser2088Ser	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
	CCDST	NR_186761.1		n.353+25710G>T		intron	N/A
	CCDST	NR_186762.1		n.179+25884G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRNR	ENST00000368801.4	TSL:1 MANE Select	c.6264C>A	p.Ser2088Ser	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
	CCDST	ENST00000420707.5	TSL:5	n.158+25857G>T		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.296+46945G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000800 AC: 9 AN: 112504 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000716

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000941

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000271

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000730

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000181 AC: 4 AN: 220510 AF XY: 0.0000329

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000309

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000301

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000234 AC: 34 AN: 1455982 Hom.: 2 Cov.: 35 AF XY: 0.0000276 AC XY: 20 AN XY: 724354

African (AFR) AF: 0.00 AC: 0 AN: 33016

American (AMR) AF: 0.00 AC: 0 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 86050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.0000298 AC: 33 AN: 1108782

Other (OTH) AF: 0.0000166 AC: 1 AN: 60110

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000888 AC: 10 AN: 112616 Hom.: 0 Cov.: 16 AF XY: 0.000111 AC XY: 6 AN XY: 54274

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000713 AC: 2 AN: 28046

American (AMR) AF: 0.0000939 AC: 1 AN: 10652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2922

East Asian (EAS) AF: 0.00 AC: 0 AN: 3358

South Asian (SAS) AF: 0.000321 AC: 1 AN: 3116

European-Finnish (FIN) AF: 0.000271 AC: 2 AN: 7392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000730 AC: 4 AN: 54788

Other (OTH) AF: 0.00 AC: 0 AN: 1460

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000533026), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-1.6
Mutation Taster		=100/0	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: rs144489730; hg19: chr1-152187841;