chr19-5824309-C-T

Variant names:

• chr19-5824309-C-T
• rs61731573
• NM_004558.5:c.144C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_004558.5(NRTN):​c.144C>T​(p.Asp48Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,606,660 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (137 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (110 hom.)
• Consequence: NRTN NM_004558.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.179
• Publications: 2 publications found

Genes affected

NRTN (HGNC:8007): (neurturin) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein signals through the RET receptor tyrosine kinase and a GPI-linked coreceptor, and promotes survival of neuronal populations. A neurturin mutation has been described in a family with Hirschsprung Disease. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 19-5824309-C-T is Benign according to our data. Variant chr19-5824309-C-T is described in ClinVar as Benign. ClinVar VariationId is 259425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.179 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004558.5. 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
	NRTN	NM_004558.5	MANE Select	c.144C>T	p.Asp48Asp	synonymous	Exon 2 of 3	NP_004549.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRTN	ENST00000303212.3	TSL:1 MANE Select	c.144C>T	p.Asp48Asp	synonymous	Exon 2 of 3	ENSP00000302648.1
	NRTN	ENST00000879152.1		c.144C>T	p.Asp48Asp	synonymous	Exon 2 of 3	ENSP00000549211.1
	NRTN	ENST00000936080.1		c.144C>T	p.Asp48Asp	synonymous	Exon 2 of 3	ENSP00000606139.1

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3502 AN: 152184 Hom.: 137 Cov.: 33

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.00597 AC: 1393 AN: 233450 AF XY: 0.00454

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000763

Gnomad OTH exome AF: 0.00174

GnomAD4 exome AF: 0.00218 AC: 3166 AN: 1454358 Hom.: 110 Cov.: 31 AF XY: 0.00182 AC XY: 1316 AN XY: 723262

African (AFR) AF: 0.0775 AC: 2590 AN: 33426

American (AMR) AF: 0.00390 AC: 171 AN: 43866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39548

South Asian (SAS) AF: 0.000152 AC: 13 AN: 85248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50364

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5760

European-Non Finnish (NFE) AF: 0.0000892 AC: 99 AN: 1110056

Other (OTH) AF: 0.00467 AC: 281 AN: 60186

GnomAD4 genome AF: 0.0230 AC: 3504 AN: 152302 Hom.: 137 Cov.: 33 AF XY: 0.0222 AC XY: 1653 AN XY: 74476

African (AFR) AF: 0.0801 AC: 3329 AN: 41544

American (AMR) AF: 0.00817 AC: 125 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68036

Other (OTH) AF: 0.0180 AC: 38 AN: 2114

Alfa AF: 0.0110 Hom.: 33

Bravo AF: 0.0260

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.3
DANN	Benign	0.82
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs61731573; hg19: chr19-5824320;