5-135535143-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006161.3(NEUROG1):c.548C>A(p.Ala183Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,609,062 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A183G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0045 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (9 hom.)
• Consequence: NEUROG1 NM_006161.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.74

Genes affected

NEUROG1 (HGNC:7764): (neurogenin 1) Enables E-box binding activity and protein homodimerization activity. Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. Predicted to be located in neuronal cell body. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005898416).
• BP6: Variant 5-135535143-G-T is Benign according to our data. Variant chr5-135535143-G-T is described in ClinVar as [Benign]. Clinvar id is 721273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEUROG1	NM_006161.3	c.548C>A	p.Ala183Glu	missense_variant	1/1	ENST00000314744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEUROG1	ENST00000314744.6	c.548C>A	p.Ala183Glu	missense_variant	1/1		NM_006161.3	P1
	ENST00000698884.1	n.496+48374G>T		intron_variant, non_coding_transcript_variant
SLC25A48	ENST00000698885.1	n.364+25387G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 684 AN: 152122 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

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: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00127 AC: 301 AN: 237500 Hom.: 1 AF XY: 0.000965 AC XY: 125 AN XY: 129550

Gnomad AFR exome AF: 0.0175

Gnomad AMR exome AF: 0.000883

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000861

GnomAD4 exome AF: 0.000502 AC: 732 AN: 1456822 Hom.: 9 Cov.: 31 AF XY: 0.000450 AC XY: 326 AN XY: 724384

Gnomad4 AFR exome AF: 0.0160

Gnomad4 AMR exome AF: 0.000946

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000775

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.00451 AC: 687 AN: 152240 Hom.: 7 Cov.: 33 AF XY: 0.00402 AC XY: 299 AN XY: 74424

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.00535

ESP6500AA AF: 0.0167 AC: 73

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00142 AC: 171

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	19
Dann	Benign	0.95
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0059	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.036	D
Polyphen		0.81	P
Vest4		0.30
MVP		0.75
MPC		0.75
ClinPred		0.014	T
GERP RS		3.1
Varity_R		0.22
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200689943; hg19: chr5-134870833;