5-135535590-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006161.3(NEUROG1):c.101G>A(p.Arg34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,591,594 control chromosomes in the GnomAD database, including 23 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (16 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (7 hom.)
• Consequence: NEUROG1 NM_006161.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.94

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066720843).
• BP6: Variant 5-135535590-C-T is Benign according to our data. Variant chr5-135535590-C-T is described in ClinVar as [Benign]. Clinvar id is 712449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00531 (809/152332) while in subpopulation AFR AF= 0.0185 (769/41586). AF 95% confidence interval is 0.0174. There are 16 homozygotes in gnomad4. There are 383 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEUROG1	NM_006161.3	c.101G>A	p.Arg34Lys	missense_variant	1/1	ENST00000314744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEUROG1	ENST00000314744.6	c.101G>A	p.Arg34Lys	missense_variant	1/1		NM_006161.3	P1
	ENST00000698884.1	n.496+48821C>T		intron_variant, non_coding_transcript_variant
SLC25A48	ENST00000698885.1	n.364+25834C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 805 AN: 152216 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00130 AC: 277 AN: 213192 Hom.: 6 AF XY: 0.00102 AC XY: 120 AN XY: 117960

Gnomad AFR exome AF: 0.0197

Gnomad AMR exome AF: 0.00109

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: 0.0000309

Gnomad OTH exome AF: 0.000372

GnomAD4 exome AF: 0.000560 AC: 806 AN: 1439262 Hom.: 7 Cov.: 31 AF XY: 0.000499 AC XY: 357 AN XY: 715616

Gnomad4 AFR exome AF: 0.0203

Gnomad4 AMR exome AF: 0.000979

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000477

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000154

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00531 AC: 809 AN: 152332 Hom.: 16 Cov.: 33 AF XY: 0.00514 AC XY: 383 AN XY: 74504

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000615 Hom.: 0

Bravo AF: 0.00624

ESP6500AA AF: 0.0149 AC: 63

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00168 AC: 201

Asia WGS AF: 0.00231 AC: 8 AN: 3478

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	16
Dann	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0067	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.98	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.27
Sift	Benign	0.15	T
Sift4G	Benign	0.86	T
Polyphen		0.61	P
Vest4		0.047
MVP		0.82
MPC		0.49
ClinPred		0.012	T
GERP RS		3.8
Varity_R		0.088
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs34137563; hg19: chr5-134871280;