NM_001009931.3:c.6555C>T

Variant names:

• chr1-152215074-G-A
• rs142300652
• NM_001009931.3:c.6555C>T

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.6555C>T​(p.Arg2185Arg) 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 0.00098 (0 hom., cov: 36)
  • Exomes 𝑓: 0.00017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.03
• Publications: 2 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=-0.93).
• BP6: Variant 1-152215074-G-A is Benign according to our data. Variant chr1-152215074-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3388416.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.03 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.6555C>T	p.Arg2185Arg	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
	CCDST	NR_186761.1		n.353+25419G>A		intron	N/A
	CCDST	NR_186762.1		n.179+25593G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRNR	ENST00000368801.4	TSL:1 MANE Select	c.6555C>T	p.Arg2185Arg	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
	CCDST	ENST00000420707.5	TSL:5	n.158+25566G>A		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.296+46654G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000942 AC: 135 AN: 143356 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000409

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: 0.0000301

Gnomad OTH AF: 0.000504

GnomAD2 exomes AF: 0.00133 AC: 136 AN: 102610 AF XY: 0.000999

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000465

Gnomad FIN exome AF: 0.000295

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.000649

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000166 AC: 242 AN: 1456344 Hom.: 0 Cov.: 127 AF XY: 0.000149 AC XY: 108 AN XY: 724560

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

African (AFR) AF: 0.00498 AC: 162 AN: 32544

American (AMR) AF: 0.000429 AC: 19 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39654

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52696

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5704

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1109472

Other (OTH) AF: 0.000549 AC: 33 AN: 60082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000976 AC: 140 AN: 143442 Hom.: 0 Cov.: 36 AF XY: 0.000985 AC XY: 69 AN XY: 70032

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

African (AFR) AF: 0.00364 AC: 131 AN: 35946

American (AMR) AF: 0.000409 AC: 6 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4854

South Asian (SAS) AF: 0.00 AC: 0 AN: 4660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000301 AC: 2 AN: 66398

Other (OTH) AF: 0.000500 AC: 1 AN: 2000

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000771 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
PhyloP100		-2.0
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs142300652; hg19: chr1-152187550; COSMIC: COSV100913782;