rs201355205

Variant names:

• chr1-108834526-T-C
• rs201355205
• NM_152763.5:c.1667A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152763.5(AKNAD1):​c.1667A>G​(p.Tyr556Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,505,254 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (1 hom.)
• Consequence: AKNAD1 NM_152763.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.342
• Publications: 0 publications found

Genes affected

AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

ENSG00000307428 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.046153545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152763.5. 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
	AKNAD1	NM_152763.5	MANE Select	c.1667A>G	p.Tyr556Cys	missense splice_region	Exon 9 of 16	NP_689976.2	Q5T1N1-1
	AKNAD1	NR_049760.2		n.1958+3024A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKNAD1	ENST00000370001.8	TSL:1 MANE Select	c.1667A>G	p.Tyr556Cys	missense splice_region	Exon 9 of 16	ENSP00000359018.3	Q5T1N1-1
	AKNAD1	ENST00000369995.7	TSL:5	c.1667A>G	p.Tyr556Cys	missense splice_region	Exon 9 of 14	ENSP00000359012.3	Q5T1N1-4
	AKNAD1	ENST00000369994.5	TSL:5	c.1577A>G	p.Tyr526Cys	missense splice_region	Exon 8 of 13	ENSP00000359011.1	Q5T1N2

Frequencies

GnomAD3 genomes AF: 0.000542 AC: 33 AN: 60844 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00102

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000387 AC: 51 AN: 131656 AF XY: 0.000324

Gnomad AFR exome AF: 0.000221

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000806

Gnomad OTH exome AF: 0.000598

GnomAD4 exome AF: 0.000435 AC: 628 AN: 1444410 Hom.: 1 Cov.: 31 AF XY: 0.000406 AC XY: 291 AN XY: 717294

African (AFR) AF: 0.0000908 AC: 3 AN: 33056

American (AMR) AF: 0.0000235 AC: 1 AN: 42526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.0000359 AC: 3 AN: 83636

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.000545 AC: 602 AN: 1104298

Other (OTH) AF: 0.000301 AC: 18 AN: 59748

GnomAD4 genome AF: 0.000542 AC: 33 AN: 60844 Hom.: 0 Cov.: 31 AF XY: 0.000605 AC XY: 17 AN XY: 28116

African (AFR) AF: 0.000258 AC: 5 AN: 19358

American (AMR) AF: 0.00 AC: 0 AN: 4592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1608

East Asian (EAS) AF: 0.00 AC: 0 AN: 2492

South Asian (SAS) AF: 0.00 AC: 0 AN: 1094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 140

European-Non Finnish (NFE) AF: 0.00102 AC: 28 AN: 27382

Other (OTH) AF: 0.00 AC: 0 AN: 704

Alfa AF: 0.000344 Hom.: 1

Bravo AF: 0.000261

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000183 AC: 21

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.7
DANN	Benign	0.64
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.34
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.078
Sift	Benign	0.12	T
Sift4G	Benign	0.17	T
Polyphen		0.92	P
Vest4		0.40
MVP		0.13
MPC		0.035
ClinPred		0.027	T
GERP RS		2.1
Varity_R		0.12
gMVP		0.16
Mutation Taster		=91/9	polymorphism

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: rs201355205; hg19: chr1-109377148;