chr10-99930339-C-A

Variant names:

• chr10-99930339-C-A
• rs79660497
• NM_015221.4:c.2261-21193G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001318326.2(DNMBP):​c.425G>T​(p.Cys142Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 550,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C142Y) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: DNMBP NM_001318326.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 0 publications found

Genes affected

DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

DNMBP-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08858931).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318326.2. 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
	DNMBP	NM_015221.4	MANE Select	c.2261-21193G>T		intron	N/A	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001318326.2		c.425G>T	p.Cys142Phe	missense	Exon 1 of 14	NP_001305255.1	A0A1B0GTX1
	DNMBP	NM_001441287.1		c.2261-21193G>T		intron	N/A	NP_001428216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.2261-21193G>T		intron	N/A	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000636706.1	TSL:2	c.425G>T	p.Cys142Phe	missense	Exon 1 of 14	ENSP00000489875.1	A0A1B0GTX1
	DNMBP	ENST00000856964.1		c.2261-21193G>T		intron	N/A	ENSP00000527023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000149 AC: 2 AN: 134508 AF XY: 0.0000137

Gnomad AFR exome AF: 0.00

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: 0.0000379

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 10 AN: 550712 Hom.: 0 Cov.: 0 AF XY: 0.0000201 AC XY: 6 AN XY: 298142

African (AFR) AF: 0.00 AC: 0 AN: 15808

American (AMR) AF: 0.00 AC: 0 AN: 34714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20030

East Asian (EAS) AF: 0.00 AC: 0 AN: 32104

South Asian (SAS) AF: 0.00 AC: 0 AN: 62776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4076

European-Non Finnish (NFE) AF: 0.0000315 AC: 10 AN: 316978

Other (OTH) AF: 0.00 AC: 0 AN: 30606

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000359 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.46
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.089	T
PhyloP100		-2.3
GERP RS		-11
Mutation Taster		=300/0	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

Other links and lift over

dbSNP: rs79660497; hg19: chr10-101690096;