NM_001080521.3:c.161C>T

Variant names:

• chr11-13009737-C-T
• rs901076428
• NM_001080521.3:c.161C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080521.3(RASSF10):​c.161C>T​(p.Ser54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,426,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: RASSF10 NM_001080521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030464172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF10	NM_001080521.3	c.161C>T	p.Ser54Leu	missense_variant	Exon 1 of 1	ENST00000529419.3	NP_001073990.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF10	ENST00000529419.3	c.161C>T	p.Ser54Leu	missense_variant	Exon 1 of 1	6	NM_001080521.3	ENSP00000485526.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000113 AC: 2 AN: 177656 Hom.: 0 AF XY: 0.0000102 AC XY: 1 AN XY: 97578

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000153

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1426634 Hom.: 0 Cov.: 31 AF XY: 0.00000283 AC XY: 2 AN XY: 706394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000532

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000456

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.161C>T (p.S54L) alteration is located in exon 1 (coding exon 1) of the RASSF10 gene. This alteration results from a C to T substitution at nucleotide position 161, causing the serine (S) at amino acid position 54 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.5
DANN	Benign	0.95
DEOGEN2	Benign	0.0056	T
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.030	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.071
MVP		0.11
GERP RS		-2.7
Varity_R		0.058
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs901076428; hg19: chr11-13031284;