NM_194312.4:c.327C>T

Variant names:

• chr2-238101973-C-T
• rs777464459
• NM_194312.4:c.327C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_194312.4(ESPNL):​c.327C>T​(p.His109His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ESPNL NM_194312.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

Genes affected

ESPNL (HGNC:27937): (espin like) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament bundle assembly and sensory perception of sound. Predicted to be located in stereocilium tip. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=2.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194312.4. 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
	ESPNL	NM_194312.4	MANE Select	c.327C>T	p.His109His	synonymous	Exon 2 of 9	NP_919288.2	Q6ZVH7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESPNL	ENST00000343063.8	TSL:2 MANE Select	c.327C>T	p.His109His	synonymous	Exon 2 of 9	ENSP00000339115.3	Q6ZVH7-1
	ESPNL	ENST00000409169.5	TSL:5	c.327C>T	p.His109His	synonymous	Exon 2 of 8	ENSP00000386577.1	Q6ZVH7-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000412 AC: 1 AN: 242806 AF XY: 0.00000754

Gnomad AFR exome AF: 0.0000657

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457802 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 725234

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5360

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111552

Other (OTH) AF: 0.00 AC: 0 AN: 60238

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs777464459; hg19: chr2-239010614;