chr15-67254917-C-T

Variant names:

• chr15-67254917-C-T
• rs140241627
• NM_001031715.3:c.21C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001031715.3(IQCH):​c.21C>T​(p.Asn7Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000651 in 1,613,884 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (1 hom.)
• Consequence: IQCH NM_001031715.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410
• Publications: 0 publications found

Genes affected

IQCH (HGNC:25721): (IQ motif containing H)

AAGAB (HGNC:25662): (alpha and gamma adaptin binding protein) The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

AAGAB Gene-Disease associations (from GenCC):

• palmoplantar keratoderma, punctate type 1A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• punctate palmoplantar keratoderma type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-67254917-C-T is Benign according to our data. Variant chr15-67254917-C-T is described in ClinVar as Benign. ClinVar VariationId is 726116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.041 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031715.3. 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
	IQCH	NM_001031715.3	MANE Select	c.21C>T	p.Asn7Asn	synonymous	Exon 1 of 21	NP_001026885.2	Q86VS3-1
	IQCH	NM_022784.3		c.21C>T	p.Asn7Asn	synonymous	Exon 1 of 6	NP_073621.2	Q86VS3-5
	IQCH	NM_001322475.2		c.-283C>T		5_prime_UTR	Exon 1 of 18	NP_001309404.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCH	ENST00000335894.9	TSL:1 MANE Select	c.21C>T	p.Asn7Asn	synonymous	Exon 1 of 21	ENSP00000336861.4	Q86VS3-1
	IQCH	ENST00000629425.2	TSL:1	c.-165C>T		5_prime_UTR	Exon 1 of 7	ENSP00000486970.1	Q86VS3-3
	IQCH	ENST00000512104.5	TSL:2	c.21C>T	p.Asn7Asn	synonymous	Exon 1 of 6	ENSP00000427323.1	Q86VS3-5

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000735 AC: 184 AN: 250486 AF XY: 0.000701

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00464

Gnomad NFE exome AF: 0.000610

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000664 AC: 971 AN: 1461536 Hom.: 1 Cov.: 30 AF XY: 0.000667 AC XY: 485 AN XY: 727066

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.000179 AC: 8 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86216

European-Finnish (FIN) AF: 0.00511 AC: 273 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000590 AC: 656 AN: 1111814

Other (OTH) AF: 0.000348 AC: 21 AN: 60374

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74500

African (AFR) AF: 0.0000721 AC: 3 AN: 41588

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00348 AC: 37 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000457 Hom.: 0

Bravo AF: 0.000264

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.77
PhyloP100		0.041
PromoterAI		-0.060	Neutral

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

Other links and lift over

dbSNP: rs140241627; hg19: chr15-67547255;