rs572461023

Variant names:

• chr11-13010013-G-A
• rs572461023
• NM_001080521.3:c.437G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-13010013-G-A
• chr11-13010013-G-C
• chr11-13010013-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080521.3(RASSF10):​c.437G>A​(p.Arg146His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,262 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R146P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RASSF10 NM_001080521.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 publications found

Genes affected

RASSF10 (HGNC:33984): (Ras association domain family member 10) Predicted to be involved in positive regulation of neural precursor cell proliferation and positive regulation of neurogenesis. Predicted to be located in cytosol; microtubule organizing center; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28484988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080521.3. 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
	RASSF10	NM_001080521.3	MANE Select	c.437G>A	p.Arg146His	missense	Exon 1 of 1	NP_001073990.2	A6NK89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF10	ENST00000529419.3	TSL:6 MANE Select	c.437G>A	p.Arg146His	missense	Exon 1 of 1	ENSP00000485526.1	A6NK89

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391262 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 685272

African (AFR) AF: 0.0000318 AC: 1 AN: 31466

American (AMR) AF: 0.00 AC: 0 AN: 35448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24888

East Asian (EAS) AF: 0.00 AC: 0 AN: 35574

South Asian (SAS) AF: 0.00 AC: 0 AN: 78630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074920

Other (OTH) AF: 0.00 AC: 0 AN: 57592

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.28	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.7
PrimateAI	Pathogenic	0.93	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.17
MVP		0.19
GERP RS		4.7
Varity_R		0.16
gMVP		0.50

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: rs572461023; hg19: chr11-13031560; COSMIC: COSV108166224; COSMIC: COSV108166224;