Genetic Variant NM_033394.3:c.3903+600A>G (chr2-159226379-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033394.3(TANC1):c.3903+600A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 153,980 control chromosomes in the GnomAD database, including 1,197 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 0.086 ( 1197 hom., cov: 33)

Exomes 𝑓: 0.020 ( 0 hom. )

Consequence

TANC1
NM_033394.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.49

Publications

3 publications found

Variant links:

Genes affected

TANC1 (HGNC:29364): (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 1) Predicted to be involved in regulation of postsynapse organization. Predicted to act upstream of or within dendritic spine maintenance; myoblast fusion; and visual learning. Predicted to be located in several cellular components, including axon terminus; neuronal cell body; and postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

TANC1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TANC1	NM_033394.3	MANE Select	c.3903+600A>G	intron	N/A	NP_203752.2	Q9C0D5-1
TANC1	NM_001350064.2		c.3882+600A>G	intron	N/A	NP_001336993.1
TANC1	NM_001350065.2		c.3882+600A>G	intron	N/A	NP_001336994.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TANC1	ENST00000263635.8	TSL:5 MANE Select	c.3903+600A>G	intron	N/A	ENSP00000263635.6	Q9C0D5-1
TANC1	ENST00000496406.1	TSL:1	n.1987A>G	non_coding_transcript_exon	Exon 1 of 2
TANC1	ENST00000851031.1		c.3957+600A>G	intron	N/A	ENSP00000521100.1

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

13121

AN:

152076

Hom.:

1195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.0729

Gnomad FIN

AF:

0.0643

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0679

GnomAD4 exome

AF:

0.0202

AC:

AN:

1784

Hom.:

Cov.:

AF XY:

0.0250

AC XY:

AN XY:

920

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.0185

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.0781

AC:

AN:

European-Finnish (FIN)

AF:

0.0345

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0155

AC:

AN:

1480

Other (OTH)

AF:

0.0227

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0863

AC:

13132

AN:

152196

Hom.:

1197

Cov.:

AF XY:

0.0885

AC XY:

6584

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.216

AC:

8967

AN:

41470

American (AMR)

AF:

0.0366

AC:

560

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0374

AC:

130

AN:

3472

East Asian (EAS)

AF:

0.228

AC:

1178

AN:

5170

South Asian (SAS)

AF:

0.0721

AC:

348

AN:

4826

European-Finnish (FIN)

AF:

0.0643

AC:

683

AN:

10624

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1035

AN:

68024

Other (OTH)

AF:

0.0691

AC:

146

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

566

1132

1699

2265

2831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0634

Hom.:

114

Bravo

AF:

0.0901

Asia WGS

AF:

0.166

AC:

578

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.012

(source)

DANN

Benign

0.34

PhyloP100

-3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over