NM_018221.5:c.-66A>C

Variant names:

• chr2-74178740-T-G
• rs2272239
• NM_018221.5:c.-66A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018221.5(MOB1A):​c.-66A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 929,788 control chromosomes in the GnomAD database, including 8,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2335 hom., cov: 31)
  • Exomes 𝑓: 0.11 (6242 hom.)
• Consequence: MOB1A NM_018221.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 2 publications found

Genes affected

MOB1A (HGNC:16015): (MOB kinase activator 1A) The protein encoded by this gene is a component of the Hippo signaling pathway, which controls organ size and tumor growth by enhancing apoptosis. Loss of the encoded protein results in cell proliferation and cancer formation. The encoded protein is also involved in the control of microtubule stability during cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOB1A	NM_018221.5	c.-66A>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000396049.5	NP_060691.2
MOB1A	NM_001317110.2	c.-66A>C		5_prime_UTR_variant	Exon 1 of 6		NP_001304039.1
MOB1A	NM_001317112.2	c.-66A>C		5_prime_UTR_variant	Exon 1 of 5		NP_001304041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOB1A	ENST00000396049.5	c.-66A>C		5_prime_UTR_variant	Exon 1 of 6	1	NM_018221.5	ENSP00000379364.3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24506 AN: 151462 Hom.: 2327 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.112 AC: 87475 AN: 778206 Hom.: 6242 Cov.: 10 AF XY: 0.112 AC XY: 42429 AN XY: 377342

African (AFR) AF: 0.200 AC: 3305 AN: 16528

American (AMR) AF: 0.297 AC: 2262 AN: 7618

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 1340 AN: 12138

East Asian (EAS) AF: 0.337 AC: 8218 AN: 24352

South Asian (SAS) AF: 0.125 AC: 2499 AN: 19954

European-Finnish (FIN) AF: 0.0881 AC: 2841 AN: 32250

Middle Eastern (MID) AF: 0.106 AC: 332 AN: 3140

European-Non Finnish (NFE) AF: 0.0992 AC: 62450 AN: 629302

Other (OTH) AF: 0.128 AC: 4228 AN: 32924

GnomAD4 genome AF: 0.162 AC: 24539 AN: 151582 Hom.: 2335 Cov.: 31 AF XY: 0.164 AC XY: 12141 AN XY: 74070

African (AFR) AF: 0.211 AC: 8708 AN: 41318

American (AMR) AF: 0.253 AC: 3853 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3458

East Asian (EAS) AF: 0.380 AC: 1942 AN: 5112

South Asian (SAS) AF: 0.142 AC: 684 AN: 4800

European-Finnish (FIN) AF: 0.0920 AC: 967 AN: 10506

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.111 AC: 7504 AN: 67852

Other (OTH) AF: 0.159 AC: 334 AN: 2102

Alfa AF: 0.149 Hom.: 362

Bravo AF: 0.183

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		0.086
PromoterAI		0.070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272239; hg19: chr2-74405867; COSMIC: COSV68517453; COSMIC: COSV68517453;