11-13009997-C-A

Variant names:

• chr11-13009997-C-A
• rs1000887892
• NM_001080521.3:c.421C>A

Variant summary

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

The NM_001080521.3(RASSF10):​c.421C>A​(p.Arg141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,446 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. R141H) 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: 1.33
• 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=0.2678057).

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.421C>A	p.Arg141Ser	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.421C>A	p.Arg141Ser	missense	Exon 1 of 1	ENSP00000485526.1	A6NK89

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392446 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 685860

African (AFR) AF: 0.00 AC: 0 AN: 31546

American (AMR) AF: 0.00 AC: 0 AN: 35552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24986

East Asian (EAS) AF: 0.00 AC: 0 AN: 35650

South Asian (SAS) AF: 0.00 AC: 0 AN: 78896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075412

Other (OTH) AF: 0.00 AC: 0 AN: 57594

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.042	T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.27	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.87	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.20
MVP		0.13
GERP RS		2.8
Varity_R		0.24
gMVP		0.67

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: rs1000887892; hg19: chr11-13031544; COSMIC: COSV108862963; COSMIC: COSV108862963;