chr6-166583971-G-C

Variant names:

• chr6-166583971-G-C
• rs3823198
• NM_001395999.1:c.*2150C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395999.1(RAMACL):​c.*2150C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: RAMACL NM_001395999.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 5 publications found

Genes affected

RAMACL (HGNC:21234): (RNA guanine-7 methyltransferase activating subunit like) Predicted to enable RNA binding activity. Predicted to be involved in methylation and recruitment of mRNA capping enzyme to RNA polymerase II holoenzyme complex. Predicted to be part of mRNA cap binding activity complex and mRNA cap methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

RPS6KA2 (HGNC:10431): (ribosomal protein S6 kinase A2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains two non-identical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternative splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2016]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395999.1. 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
	RAMACL	NM_001395999.1	MANE Select	c.*2150C>G		3_prime_UTR	Exon 1 of 1	NP_001382928.1	A0A3B3IU46
	RPS6KA2	NM_021135.6	MANE Select	c.99+42950C>G		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.175-45187C>G		intron	N/A	NP_001305865.2	F2Z2J1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMACL	ENST00000444122.3	TSL:6 MANE Select	c.*2150C>G		3_prime_UTR	Exon 1 of 1	ENSP00000498060.1	A0A3B3IU46
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.99+42950C>G		intron	N/A	ENSP00000265678.4	Q15349-1
	RPS6KA2	ENST00000510118.5	TSL:2	c.175-45187C>G		intron	N/A	ENSP00000422435.1	F2Z2J1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.25
PhyloP100		-1.1

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: rs3823198; hg19: chr6-166997459;