NM_052876.4:c.21G>T

Variant names:

• chr19-13135228-G-T
• NM_052876.4:c.21G>T

Variant summary

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

The NM_052876.4(NACC1):​c.21G>T​(p.Met7Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,550 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NACC1 NM_052876.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17

Genes affected

NACC1 (HGNC:20967): (nucleus accumbens associated 1) This gene encodes a member of the BTB/POZ protein family. BTB/POZ proteins are involved in several cellular processes including proliferation, apoptosis and transcription regulation. The encoded protein is a transcriptional repressor that plays a role in stem cell self-renewal and pluripotency maintenance. The encoded protein also suppresses transcription of the candidate tumor suppressor Gadd45GIP1, and expression of this gene may play a role in the progression of multiple types of cancer. A pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Feb 2012]

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=0.16410884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NACC1	NM_052876.4	c.21G>T	p.Met7Ile	missense_variant	Exon 2 of 6	ENST00000292431.5	NP_443108.1
NACC1	XM_005259721.4	c.21G>T	p.Met7Ile	missense_variant	Exon 3 of 7		XP_005259778.1
NACC1	XM_047438118.1	c.21G>T	p.Met7Ile	missense_variant	Exon 2 of 6		XP_047294074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NACC1	ENST00000292431.5	c.21G>T	p.Met7Ile	missense_variant	Exon 2 of 6	1	NM_052876.4	ENSP00000292431.3
NACC1	ENST00000586171.3	c.21G>T	p.Met7Ile	missense_variant	Exon 3 of 7	5		ENSP00000467120.2
NACC1	ENST00000700232.1	c.21G>T	p.Met7Ile	missense_variant	Exon 2 of 6			ENSP00000514870.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456550 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0051	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.00052
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	.;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.53	.;N
REVEL	Benign	0.11
Sift	Benign	0.60	.;T
Sift4G	Benign	0.46	T;T
Polyphen		0.0060	.;B
Vest4		0.33
MutPred		0.59		Loss of disorder (P = 0.0736);Loss of disorder (P = 0.0736);
MVP		0.40
MPC		1.3
ClinPred		0.42	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.50
gMVP		0.79

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-13246042;