1-37501927-T-C

Position:

• chr1-37501927-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270875.3(MEAF6):​c.410A>G​(p.Gln137Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEAF6 NM_001270875.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86

Genes affected

MEAF6 (HGNC:25674): (MYST/Esa1 associated factor 6) This gene encodes a nuclear protein involved in transcriptional activation. The encoded protein may form a component of several different histone acetyltransferase complexes. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

MEAF6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22299168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEAF6	NM_001270875.3	c.410A>G	p.Gln137Arg	missense_variant	5/7	ENST00000296214.10	NP_001257804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEAF6	ENST00000296214.10	c.410A>G	p.Gln137Arg	missense_variant	5/7	1	NM_001270875.3	ENSP00000296214.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.410A>G (p.Q137R) alteration is located in exon 5 (coding exon 5) of the MEAF6 gene. This alteration results from a A to G substitution at nucleotide position 410, causing the glutamine (Q) at amino acid position 137 to be replaced by an arginine (R). 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	0.15
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	.;T;.;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N;N;.;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.071	T;T;T;T;T
Sift4G	Benign	0.24	T;T;T;T;T
Polyphen		0.96	D;P;P;.;P
Vest4		0.43
MutPred		0.29		Gain of glycosylation at S136 (P = 0.0729);Gain of glycosylation at S136 (P = 0.0729);.;Gain of glycosylation at S136 (P = 0.0729);Gain of glycosylation at S136 (P = 0.0729);
MVP		0.39
MPC		0.88
ClinPred		0.72	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-37967528;